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plasticity of human protein disulfide isomerase: evidence for mobility around the x-linker region and its functional significance.protein disulfide isomerase (pdi), which consists of multiple domains arranged as abb'xa'c, is a key enzyme responsible for oxidative folding in the endoplasmic reticulum. in this work we focus on the conformational plasticity of this enzyme. proteolysis of native human pdi (hpdi) by several proteases consistently targets sites in the c-terminal half of the molecule (x-linker and a' domain) leaving large fragments in which the n terminus is intact. fluorescence studies on the w111f/w390f mutant ...201020516074
bat3 promotes the membrane integration of tail-anchored proteins.the membrane integration of tail-anchored proteins at the endoplasmic reticulum (er) is post-translational, with different tail-anchored proteins exploiting distinct cytosolic factors. for example, mammalian trc40 has a well-defined role during delivery of tail-anchored proteins to the er. although its saccharomyces cerevisiae equivalent, get3, is known to function in concert with at least four other components, get1, get2, get4 and get5 (mdy2), the role of additional mammalian proteins during t ...201020516149
the fanconi anemia protein, fancg, binds to the ercc1-xpf endonuclease via its tetratricopeptide repeats and the central domain of ercc1.there is evidence that fanconi anemia (fa) proteins play an important role in the repair of dna interstrand cross-links (icls), but the precise mechanism by which this occurs is not clear. one of the critical steps in the icl repair process involves unhooking of the cross-link from dna by incisions on one strand on either side of the icl and its subsequent removal. the ercc1-xpf endonuclease is involved in this unhooking step and in the removal of the cross-link. we have previously shown that se ...201020518486
[polar steroids from solaster endeca starfish and the physiological activity of polar steroids from three starfish species].four polyhydroxylated steroids, new (20r)-5alpha-cholestan-3beta,6alpha,8,15alpha,24,26-hexaol (i) and known (20r,25s)-5alpha-cholestan-3beta6alpha,8,15beta,16beta,26-hexaol, (20r,25s)-5alpha-cholestan-3beta,6alpha,15beta,16beta,26-pentaol, and marthasterone sulfate were isolated from the solaster endeca starfish inhabiting the sea of okhotsk and characterized. steroid (i) contains a 24,26-dihydroxylated side chain, which is uncommon for starfish polyols. the isolated steroids and related metabo ...201020531484
molecular bridging of aging and cancer: a carf link.collaborator of arf (carf) was first cloned as an arf partner in yeast two-hybrid screens. it enhances arf-dependent and -independent p53 functions, which are central to the control of cell growth and tumor suppression in human cells. carf interacts with arf, p53, and mdm2 proteins, and in turn gets regulated by mdm2-mediated degradation, suggesting a self-regulatory loop. carf is upregulated during replicative, oncogenic, and stress-induced senescence. overexpression of carf induced premature s ...201020536841
the jmjn domain of jhd2 is important for its protein stability, and the plant homeodomain (phd) finger mediates its chromatin association independent of h3k4 methylation.histone lysine methylation is a dynamic process that plays an important role in regulating chromatin structure and gene expression. recent studies have identified jhd2, a jmjc domain-containing protein, as an h3k4-specific demethylase in budding yeast. however, important questions regarding the regulation and functions of jhd2 remain unanswered. in this study, we show that jhd2 has intrinsic activity to remove all three states of h3k4 methylation in vivo and can dynamically associate with chroma ...201020538609
predicting genetic modifier loci using functional gene networks.most phenotypes are genetically complex, with contributions from mutations in many different genes. mutations in more than one gene can combine synergistically to cause phenotypic change, and systematic studies in model organisms show that these genetic interactions are pervasive. however, in human association studies such nonadditive genetic interactions are very difficult to identify because of a lack of statistical power--simply put, the number of potential interactions is too vast. one appro ...201020538624
nutrient regulation of mtorc1 and cell growth. 201020543582
the c-terminal alpha-alpha superhelix of pat is required for mrna decapping in metazoa.pat proteins regulate the transition of mrnas from a state that is translationally active to one that is repressed, committing targeted mrnas to degradation. pat proteins contain a conserved n-terminal sequence, a proline-rich region, a mid domain and a c-terminal domain (pat-c). we show that pat-c is essential for the interaction with mrna decapping factors (i.e. dcp2, edc4 and lsm1-7), whereas the p-rich region and mid domain have distinct functions in modulating these interactions. dcp2 and e ...201020543818
alpha4 phosphoprotein interacts with edd e3 ubiquitin ligase and poly(a)-binding protein.mammalian alpha4 phosphoprotein, the homolog of yeast tap42, is a component of the mammalian target-of-rapamycin (mtor) pathway that regulates ribogenesis, the initiation of translation, and cell-cycle progression. alpha4 is known to interact with the catalytic subunit of protein phosphatase 2a (pp2ac) and to regulate pp2a activity. using alpha4 as bait in yeast two-hybrid screening of a human k562 erythroleukemia cdna library, edd (e3 isolated by differential display) e3 ubiquitin ligase was id ...201020544796
expression, purification and characterization of the cancer-germline antigen gage12i: a candidate for cancer immunotherapy.gage cancer-germline antigens are frequently expressed in a broad range of different cancers, while their expression in normal tissues is limited to the germ cells of the immune privileged organs, testis and ovary. gage proteins are immunogenic in humans, which make them promising targets for immunotherapy and candidates for cancer vaccines. recombinant proteins may be superior to peptides as immunogens, since they have the potential to prime both cd4(+) and cd8(+) t cells and are not dependent ...201020546897
the production, characterisation and enhanced pharmacokinetics of scfv-albumin fusions expressed in saccharomyces cerevisiae.an expression system is described for the production of monomeric scfvs and scfv antibody fragments genetically fused to human albumin (at either the n- or c-terminus or both). based upon strains of saccharomyces cerevisiae originally developed for the production of a recombinant human albumin (recombumin) this system has delivered high levels of secreted product into the supernatant of shake flask and high cell density fed-batch fermentations. specific binding to the corresponding ligand was de ...201020546898
the sarcomeric z-disc component myopodin is a multiadapter protein that interacts with filamin and alpha-actinin.here we introduce myopodin as a novel filamin c binding partner. corroborative yeast two-hybrid and biochemical analyses indicate that the central part of myopodin that shows high homology to the closely related protein synaptopodin and that is common to all its currently known or predicted variants interacts with filamin c immunoglobulin-like domains 20-21. a detailed characterization of the previously described interaction between myopodin and alpha-actinin demonstrates for the first time that ...201020554076
intramembrane proteolysis of mgm1 by the mitochondrial rhomboid protease is highly promiscuous regarding the sequence of the cleaved hydrophobic segment.rhomboids are a family of intramembrane serine proteases that are conserved in bacteria, archaea, and eukaryotes. they are required for numerous fundamental cellular functions such as quorum sensing, cell signaling, and mitochondrial dynamics. mitochondrial rhomboids form an evolutionarily distinct class of rhomboids. it is largely unclear how their activity is controlled and which substrate determinants are responsible for recognition and cleavage. we investigated these requirements for the mit ...201020558178
[lass2 interacts with v-atpase and inhibits cell growth of hepatocellular carcinoma].homo sapiens longevity assurance homologue 2 (lass2) is a novel gene isolated from a human liver cdna library by our laboratory, and it is a human homologue of the yeast longevity assurance gene lag1 (saccharomyces cerevisiae longevity assurance gene). according to our previous results, lass2 could interact with subunit c of vacuolar type h(+)-atpase (v-atpase), and the overexpression of lass2 could inhibit the cell growth of a human hepatocellular carcinoma (hcc) cell line, smmc-7721. in order ...201020571735
streptococcus mutans inhibits candida albicans hyphal formation by the fatty acid signaling molecule trans-2-decenoic acid (sdsf).in the human mouth, fungi and several hundred species of bacteria coexist. here we report a case of interkingdom signaling in the oral cavity: a compound excreted by the caries bacterium streptococcus mutans inhibits the morphological transition from yeast to hyphae, an important virulence trait, in the opportunistic fungus candida albicans. the compound excreted by s. mutans was originally studied because it inhibited signaling by the universal bacterial signal autoinducer-2 (ai-2), determined ...201020572249
the cellular rna helicase ddx1 interacts with coronavirus nonstructural protein 14 and enhances viral replication.the involvement of host proteins in the replication and transcription of viral rna is a poorly understood area for many rna viruses. for coronaviruses, it was long speculated that replication of the giant rna genome and transcription of multiple subgenomic mrna species by a unique discontinuous transcription mechanism may require host cofactors. to search for such cellular proteins, yeast two-hybrid screening was carried out by using the nonstructural protein 14 (nsp14) from the coronavirus infe ...201020573827
the closely related rna helicases, uap56 and urh49, preferentially form distinct mrna export machineries and coordinately regulate mitotic progression.nuclear export of mrna is an essential process for eukaryotic gene expression. the trex complex couples gene expression from transcription and splicing to mrna export. sub2, a core component of the trex complex in yeast, has diversified in humans to two closely related rna helicases, uap56 and urh49. here, we show that urh49 forms a novel urh49-cip29 complex, termed the arex (alternative mrna export) complex, whereas uap56 forms the human trex complex. the mrnas regulated by these helicases are ...201020573985
estrogenic pyrethroid pesticides regulate expression of estrogen receptor transcripts in mouse sertoli cells differently from 17beta-estradiol.studies suggested that exposure to agricultural pesticides may affect male fertility. pyrethroids are widely used pesticides due to their insecticidal potency and low mammalian toxicity. a recombinant yeast assay system incorporating the human alpha-estrogen receptor was used to analyze the estrogenicity of a range of readily available pyrethroid pesticides. the commercial product ripcord plus showed estrogenic activity by this assay. to determine whether pyrethroid compounds might exert an effe ...201020574910
long-term conservation of hcv rna at 4 degrees c using a new rna stabilizing solution.protecting rna from degradation, whilst maintaining its biological activity, is essential in molecular biology. however, rna is very sensitive to degradation by ribonucleases, especially at temperatures above 0 degrees c. the stability of rna was examined at 4 degrees c and -20 degrees c, in a new stabilizing solution consisting of a low-molarity mixture of chaotropic agents guanidinium and ammonium thiocyanate, a buffer for ph stabilization, phenol, and yeast rna. two substrates were tested for ...201020576506
the genemania prediction server: biological network integration for gene prioritization and predicting gene function.genemania (http://www.genemania.org) is a flexible, user-friendly web interface for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. given a query list, genemania extends the list with functionally similar genes that it identifies using available genomics and proteomics data. genemania also reports weights that indicate the predictive value of each selected data set for the query. six organisms are currently supported (arabidopsis thal ...201020576703
simple is good: yeast models of neurodegeneration.the budding yeast, saccharomyces cerevisiae, is the best-studied eukaryotic cell, at both genetic and physiological levels. as a eukaryote, yeast shares highly conserved molecular and cellular mechanisms with human cells. thus, this simple fungus is an invaluable model to study the fundamental molecular mechanisms involved in several human diseases. in the particular case of neurodegenerative disorders, yeast models have been able to recapitulate several important features of complex and devasta ...201020579105
recombinant form of human wild type mannan-binding lectin (mbl/a) but not its structural variant (mbl/c) promotes phagocytosis of zymosan by activating complement.mannan-binding lectin (mbl) mediates innate immune responses, such as activation of the complement lectin pathway and phagocytosis, to help fight infections. in the present study, employing recombinant forms of human mbl (rmbl), the role of wild type mbl (rmbl/a) and its structural variant rmbl/c in mediating thp-1 phagocytosis of fluorescent-labeled zymosan was examined and compared to mbl purified from human plasma (pmbl/a). flow cytometric analyses revealed that opsonization of zymosan with r ...201020579738
antimicrobial activity of mucosal-associated invariant t cells.mucosal-associated invariant t lymphocytes (mait lymphocytes) are characterized by two evolutionarily conserved features: an invariant t cell antigen receptor (tcr) alpha-chain and restriction by the major histocompatibility complex (mhc)-related protein mr1. here we show that mait cells were activated by cells infected with various strains of bacteria and yeast, but not cells infected with virus, in both humans and mice. this activation required cognate interaction between the invariant tcr and ...201020581831
synergy of caspofungin with human polymorphonuclear granulocytes for killing candida albicans.the influence of caspofungin on polymorphonuclear leukocyte (pmn) phagocytosis and intracellular killing of candida albicans was investigated. caspofungin, at all of the concentrations tested (2, 3.2, and 8 microg/ml), significantly increased intracellular killing by pmns through its direct action on both yeast cells and pmns, indicating the potential ability of caspofungin to synergize with phagocytes for candidal killing. caspofungin may therefore constitute an effective therapeutic option for ...201020585121
engineering of glycosylation in yeast and other fungi: current state and perspectives.with the increasing demand for recombinant proteins and glycoproteins, research on hosts for producing these proteins is focusing increasingly on more cost-effective expression systems. yeasts and other fungi are promising alternatives because they provide easy and cheap systems that can perform eukaryotic post-translational modifications. unfortunately, yeasts and other fungi modify their glycoproteins with heterogeneous high-mannose glycan structures, which is often detrimental to a therapeuti ...201020585772
identification of the transactivation domain of the human fhl3.four and a half lim domain protein 3 (fhl3) has the transactivation and repressor activity, and plays important roles in regulating the expression levels of various genes. in this study, fhl3 was proved to possess the auto-activation ability when constructed into the pgbkt7 plasmid (a gala dna-binding domain (bd) cloning vector of the yeast two-hybrid system) and transformed into yeast y190 cells. to determine the transactivation domain of fhl3, five mutants were constructed by sequentially dele ...201020586194
functional characterization of aibp, a novel aurora-a binding protein in centrosome structure and spindle formation.aurora-a is involved in chromosome alignment, centrosome maturation, mitotic spindle assembly and regards to an oncogene. aurora-a is also known to bind to several other proteins affecting its up-regulation or down-regulation and localization. however, how these different binding signals work together to regulate aurora-a is not properly known. to explore more aurora-a interacting proteins, the low-copy yeast two-hybrid screening using aurora-a as bait protein was performed. one novel gene, aibp ...201020596670
structure-mutagenicity relationship of kaurenoic acid from xylopia sericeae (annonaceae).kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. in this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (ka), i.e. (-)-kaur-16-en-19-oic acid, isolated from xylopia sericeae st. hill, using several ...201020599626
a decade of systems biology.systems biology provides a framework for assembling models of biological systems from systematic measurements. since the field was first introduced a decade ago, considerable progress has been made in technologies for global cell measurement and in computational analyses of these data to map and model cell function. it has also greatly expanded into the translational sciences, with approaches pioneered in yeast now being applied to elucidate human development and disease. here, we review the sta ...201020604711
the emerging role of vhs domain-containing tom1, tom1l1 and tom1l2 in membrane trafficking.the maintenance of cellular homeostasis and execution of regulatory mechanisms to dynamically govern various cellular processes require the correct delivery of proteins to their target subcellular compartments. it is estimated that over 30% of the proteins encoded by the human genome, projected to encode about 25 000 proteins and other macromolecules, are delivered to the secretory and endocytic pathways where movement of proteins between various compartments is primarily mediated by vesicles/ca ...201020604899
the saccharomyces cerevisiae swi/snf complex can catalyze formation of dimeric nucleosome structures in vitro.the swi/snf chromatin-remodeling complexes, human baf/pbaf and yeast rsc, can catalyze formation of stably altered dimeric forms of nucleosomes. however, the ability to create remodeled dimers has not yet been reported for the saccharomyces cerevisiae swi/snf complex. despite its similarity with the other swi/snf proteins, the yeast swi/snf complex features certain structural and functional differences. this raises the question of whether yswi/snf can in fact catalyze formation of dimeric nucleo ...201020608642
purification of functional human cl(-)/hco(3)(-) exchanger, ae1, over-expressed in saccharomyces cerevisiae.there is no high-resolution structure for the membrane domain of the human erythrocyte anion exchanger, ae1 (band 3). in this report, we have developed an expression and purification strategy for ae1 to be used in crystallization trials. saccharomyces cerevisiae strain bj5457 was transformed with an expression vector encoding the ae1 membrane domain (ae1md, amino acids 388-911), fused c-terminally to an epitope tag, corresponding to the nine c-terminal amino acids of rhodopsin. the fusion protei ...201020609390
experimental annotation of the human pathogen candida albicans coding and noncoding transcribed regions using high-resolution tiling arrays.compared to other model organisms and despite the clinical relevance of the pathogenic yeast candida albicans, no comprehensive analysis has been done to provide experimental support of its in silico-based genome annotation.201020618945
relocation of the chromosomal passenger complex prevents mitotic checkpoint engagement at anaphase.the mitotic checkpoint monitors the attachment of kinetochores to microtubules and delays anaphase onset until all sister kinetochores have become attached to opposite poles [1, 2]. correct bipolar attachment leads to kinetochore deformation and tension and satisfies the checkpoint [3-6]. what prevents mitotic checkpoint reactivation when sister centromeres are split and tension is lost at anaphase onset? aurora b kinase, the catalytic subunit of the chromosomal passenger protein complex (cpc) [ ...201020619651
proteogenomics to discover the full coding content of genomes: a computational perspective.proteogenomics has emerged as a field at the junction of genomics and proteomics. it is a loose collection of technologies that allow the search of tandem mass spectra against genomic databases to identify and characterize protein-coding genes. proteogenomic peptides provide invaluable information for gene annotation, which is difficult or impossible to ascertain using standard annotation methods. examples include confirmation of translation, reading-frame determination, identification of gene a ...201020620248
a screening method tuned for mrna processing factors in human cells by evaluation of the luciferase reporter activity and the subcellular distribution of bulk poly(a)+ rna.screening of mrna export factors in saccharomyces cerevisiae and drosophila melanogaster has identified a number of mrna processing factors involved in multiple mrna processing steps. however, only limited information is available on human cells. here we established a screening system searching for mrna processing factors in human cells by combining the luciferase reporter system and fluorescence in situ hybridization, which evaluates the nuclear/cytoplasmic distribution of bulk poly(a)+ rna. th ...201020622428
the collagen v homotrimer [alpha1(v)](3) production is unexpectedly favored over the heterotrimer [alpha1(v)](2)alpha2(v) in recombinant expression systems.collagen v, a fibrillar collagen with important functions in tissues, assembles into distinct chain associations. the most abundant and ubiquitous molecular form is the heterotrimer [alpha1(v)](2)alpha2(v). in the attempt to produce high levels of recombinant collagen v heterotrimer for biomedical device uses, and to identify key factors that drive heterotrimeric chain association, several cell expression systems (yeast, insect, and mammalian cells) have been assayed by cotransfecting the human ...201020625483
the migration of mitochondrial dna fragments to the nucleus affects the chronological aging process of saccharomyces cerevisiae.migration of fragmented mitochondrial dna (mtdna) to the nucleus has been shown to occur in multiple species including yeast, plants, and mammals. several human diseases, including pallister-hall syndrome and mucolipidosis, can be initiated by mtdna insertion mutagenesis of nuclear dna. in yeast, we demonstrated that the rate of mtdna fragments translocating to the nucleus increases during chronological aging. the yeast chronological lifespan (cls) is determined by the survival of nondividing ce ...201020626726
learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in saccharomyces cerevisiae and homo sapiens.dna in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. the precise positioning of the nucleosome cores allows for selective access to the dna, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. we describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri- ...201020628623
the classical swine fever virus n-terminal protease n(pro) binds to cellular hax-1.the positive-stranded rna genome of classical swine fever virus (csfv) encodes 12 known proteins. the first protein to be translated is the n-terminal protease (n(pro)). n(pro) helps evade the innate interferon response by targeting interferon regulatory factor-3 for proteasomal degradation and also participates in the evasion of dsrna-induced apoptosis. to elucidate the mechanisms by which n(pro) functions, we performed a yeast two-hybrid screen in which the anti-apoptotic protein hax-1 was ide ...201020631090
telomeres: structures in need of unwinding.telomeres protect the ends of eukaryotic chromosomes from being recognized and processed as double strand breaks. in most organisms, telomeric dna is highly repetitive with a high gc-content. moreover, the g residues are concentrated in the strand running 3'-5' from the end of the chromosome towards its center. this g-rich strand is extended to form a 3' single-stranded tail that can form unusual secondary structures such as t-loops and g-quadruplex dna. both the duplex repeats and the single-st ...201020637196
linking h3k79 trimethylation to wnt signaling through a novel dot1-containing complex (dotcom).epigenetic modifications of chromatin play an important role in the regulation of gene expression. kmt4/dot1 is a conserved histone methyltransferase capable of methylating chromatin on lys79 of histone h3 (h3k79). here we report the identification of a multisubunit dot1 complex (dotcom), which includes several of the mixed lineage leukemia (mll) partners in leukemia such as enl, af9/mllt3, af17/mllt6, and af10/mllt10, as well as the known wnt pathway modifiers trrap, skp1, and beta-catenin. we ...201020203130
extensive proteomic screening identifies the obesity-related nyggf4 protein as a novel lrp1-interactor, showing reduced expression in early alzheimer's disease.abstract:201020205790
interaction between hhex and sox13 modulates wnt/tcf activity.fine-tuning of the wnt/tcf pathway is crucial for multiple embryological processes, including liver development. here we describe how the interaction between hhex (hematopoietically expressed homeobox) and sox13 (sry-related high mobility group box transcription factor 13), modulates wnt/tcf pathway activity. hhex is a homeodomain factor expressed in multiple endoderm-derived tissues, like the liver, where it is essential for proper development. the pleiotropic expression of hhex during embryoni ...201020028982
the human carnitine transporter slc22a16 mediates high affinity uptake of the anticancer polyamine analogue bleomycin-a5.bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. however, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. previously, we documented that the saccharomyces cerevisiae l-carnitine transporter agp2 is responsible for the high affinity uptake of polyamines and of the polyamine an ...201020037140
mtor binds to the promoters of rna polymerase i- and iii-transcribed genes.target of rapamycin (tor) is a conserved regulator of gene expression from yeast to humans. in budding yeast, tor is associated with ribosomal dna (rdna) promoter, which is critical for ribosome biogenesis and transfer rna (trna) synthesis. whether mtor behaves similarly in mammalian cells is unknown. here, we report that mtor is detected at several different promoters in human and murine cells, including that of rdna and trna genes. the association of mtor with these promoters is regulated by g ...201020038818
appl1 is dispensable for mouse development, and loss of appl1 has growth factor-selective effects on akt signaling in murine embryonic fibroblasts.the adaptor protein appl1 (adaptor protein containing pleckstrin homology (ph), phosphotyrosine binding (ptb), and leucine zipper motifs) was first identified as a binding protein of akt2 by yeast two-hybrid screening. appl1 was subsequently found to bind to several membrane-bound receptors and was implicated in their signal transduction through akt and/or mapk pathways. to determine the unambiguous role of appl1 in vivo, we generated appl1 knock-out mice. here we report that appl1 knock-out mic ...201020040596
cell-penetrating dna-binding protein as a safe and efficient naked dna delivery carrier in vitro and in vivo.non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. using the novel, human-origin hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked dna in vitro and in vivo. the new dna delivery system contains hph-1-gal4 dna-binding domain (dbd) fusion protein and enhanced green fluorescent protein (egfp ...201020043881
structure of trypanosoma brucei glutathione synthetase: domain and loop alterations in the catalytic cycle of a highly conserved enzyme.glutathione synthetase catalyses the synthesis of the low molecular mass thiol glutathione from l-gamma-glutamyl-l-cysteine and glycine. we report the crystal structure of the dimeric enzyme from trypanosoma brucei in complex with the product glutathione. the enzyme belongs to the atp-grasp family, a group of enzymes known to undergo conformational changes upon ligand binding. the t. brucei enzyme crystal structure presents two dimers in the asymmetric unit. the structure reveals variability in ...201020045436
the parl family of mitochondrial rhomboid proteases.rhomboids are an ancient and conserved family of intramembrane-cleaving proteases, a small group of proteolytic enzymes capable of hydrolyzing a peptide bond within a transmembrane helix that anchors a substrate protein to the membrane. mitochondrial rhomboids evolved in eukaryotes to coordinate a critical aspect of cell biology, the regulation of mitochondrial membranes dynamics. this function appears to have required the emergence of a structural feature that is unique among all other rhomboid ...201020045481
probiotic table olives: microbial populations adhering on olive surface in fermentation sets inoculated with the probiotic strain lactobacillus paracasei impc2.1 in an industrial plant.this study reports the dynamics of microbial populations adhering on the surface of debittered green olives cv. bella di cerignola in fermentation sets inoculated with the probiotic strain lactobacillus paracasei impc2.1 in different brining conditions (4% and 8% (w/v) nacl) at room temperature and 4 degrees c. the probiotic strain successfully colonized the olive surface dominating the natural lab population and decreasing the ph of brines to <or=5.0 after 30 days until the end of fermentation. ...201020226556
the tango of histone marks and chaperones at replication fork.nucleosomes are disassembled during dna replication. how histone modifications and histone chaperones collaborate to reassemble nucleosomes on replicated dna is explored by jasencakova et al. (2010) and burgess et al. (2010) in this and a recent issue of molecular cell, respectively.201020227364
dnase i hypersensitivity and epsilon-globin transcriptional enhancement are separable in locus control region (lcr) hs1 mutant human beta-globin yac transgenic mice.expression of the five beta-like globin genes (epsilon, ggamma, agamma, delta, beta) in the human beta-globin locus depends on enhancement by the locus control region, which consists of five dnase i hypersensitive sites (5'hs1 through 5'hs5). we report here a novel enhancer activity in 5'hs1 that appears to be potent in transfected k562 cells. deletion analyses identified a core activating element that bound to gata-1, and a two-nucleotide mutation that disrupted gata-1 binding in vitro abrogate ...201020231293
sequence characterization and promoter identification of porcine apc10 gene.apc10 protein, a subunit of the anaphase-promoting complex (apc), plays an essential role in the progression of cells from mitosis to g1. in this study, we cloned and sequenced partial cdna, intron 1 and 5'-flanking sequences of porcine apc10. the partial cdna is 595 bp long and has an open reading frame of 558 bp which encodes 185 putative amino acids. real-time pcr analysis revealed that the porcine apc10 mrna expression shows a wide distribution and expression levels varies within a small dif ...201020232159
conquering the complex world of human septins: implications for health and disease.septins are highly conserved filamentous proteins first characterized in budding yeast and subsequently identified in must eukaryotes. septins can bind and hydrolyze gtp, which is intrinsically related to their formation of septin hexamers and functional protein interactions. the human septin family is composed of 14 loci, sept1-sept14, which encode dozens of different septin proteins. their central gtpase and polybasic domain regions are highly conserved but they diverge in their n-terminus and ...201020236126
topological network alignment uncovers biological function and phylogeny.sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology and disease. comparison and alignment of biological networks will probably have a similar impact. existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. in this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. we appl ...201020236959
comprehensive screening of human genes with inhibitory effects on yeast growth and validation of a yeast cell-based system for screening chemicals.to evaluate yeast as a high-throughput cell-based system for screening chemicals that may lead to drug development, 10,302 full-length human cdnas (~50% of the total cdnas) were introduced into yeast. approximately 5.6% (583 clones) of the cdnas repressed the growth of yeast. notably, ~25% of the repressive cdnas encoded uncharacterized proteins. small chemicals can be readily surveyed by monitoring their restorative effects on the growth of yeast. the authors focused on protein kinases because ...201020237203
the fission yeast inhibitor of growth (ing) protein png1p functions in response to dna damage.in budding yeast and human cells, ing (inhibitor of growth) tumor suppressor proteins play important roles in response to dna damage by modulating chromatin structure through collaborating with histone acetyltransferase or histone deacetylase complexes. however, the biological functions of ing family proteins in fission yeast are poorly defined. here, we report that png1p, a fission yeast ing homolog protein, is required for cell growth under normal and dna-damaged conditions. png1p was further ...201020299455
genetic studies of human dna repair proteins using yeast as a model system.understanding the roles of human dna repair proteins in genetic pathways is a formidable challenge to many researchers. genetic studies in mammalian systems have been limited due to the lack of readily available tools including defined mutant genetic cell lines, regulatory expression systems, and appropriate selectable markers. to circumvent these difficulties, model genetic systems in lower eukaryotes have become an attractive choice for the study of functionally conserved dna repair proteins a ...201020300059
systematic discovery of nonobvious human disease models through orthologous phenotypes.biologists have long used model organisms to study human diseases, particularly when the model bears a close resemblance to the disease. we present a method that quantitatively and systematically identifies nonobvious equivalences between mutant phenotypes in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). these orthologous phenotypes, or phenologs, predict unique genes associated with diseases. ou ...201020308572
novel interactors and a role for supervillin in early cytokinesis.supervillin, the largest member of the villin/gelsolin/flightless family, is a peripheral membrane protein that regulates each step of cell motility, including cell spreading. most known interactors bind within its amino (n)-terminus. we show here that the supervillin carboxy (c)-terminus can be modeled as supervillin-specific loops extending from gelsolin-like repeats plus a villin-like headpiece. we have identified 27 new candidate interactors from yeast two-hybrid screens. the interacting seq ...201020309963
ptph1 dephosphorylates and cooperates with p38gamma mapk to increase ras oncogenesis through pdz-mediated interaction.protein phosphatases are believed to coordinate with kinases to execute biological functions, but examples of such integrated activities, however, are still missing. in this report, we have identified protein tyrosine phosphatase h1 (ptph1) as a specific phosphatase for p38gamma mitogen-activated protein kinase (mapk) and shown their cooperative oncogenic activity through direct binding. p38gamma, a ras effector known to act independent of its phosphorylation, was first shown to require its uniq ...201020332238
the legionella pneumophila f-box protein lpp2082 (ankb) modulates ubiquitination of the host protein parvin b and promotes intracellular replication.the environmental pathogen legionella pneumophila encodes three proteins containing f-box domains and additional protein-protein interaction domains, reminiscent of eukaryotic scf ubiquitin-protein ligases. here we show that the f-box proteins of l. pneumophila strain paris are dot/icm effectors involved in the accumulation of ubiquitinated proteins associated with the legionella-containing vacuole. single, double and triple mutants of the f-box protein encoding genes were impaired in infection ...201020345489
integrating gene expression and go classification for pca by preclustering.gene expression data can be analyzed by summarizing groups of individual gene expression profiles based on go annotation information. the mean expression profile per group can then be used to identify interesting go categories in relation to the experimental settings. however, the expression profiles present in go classes are often heterogeneous, i.e., there are several different expression profiles within one class. as a result, important experimental findings can be obscured because the summar ...201020346140
structural and biochemical characterization of yeast monothiol glutaredoxin grx6.glutaredoxins (grxs) are a ubiquitous family of proteins that reduce disulfide bonds in substrate proteins using electrons from reduced glutathione (gsh). the yeast saccharomyces cerevisiae grx6 is a monothiol grx that is localized in the endoplasmic reticulum and golgi compartments. grx6 consists of three segments, a putative signal peptide (m1-i36), an n-terminal domain (k37-t110), and a c-terminal grx domain (k111-n231, designated grx6c). compared to the classic dithiol glutaredoxin grx1, grx ...201020347849
selection of rna aptamers imported into yeast and human mitochondria.in the yeast saccharomyces cerevisiae, nuclear dna-encoded is partially imported into mitochondria. we previously found that the synthetic transcripts of yeast trna(lys) and a number of their mutant versions could be specifically internalized by isolated yeast and human mitochondria. the mitochondrial targeting of trna(lys) in yeast was shown to depend on the cytosolic precursor of mitochondrial lysyl-trna synthetase and the glycolytic enzyme enolase. here we applied the approach of in vitro sel ...201020348443
triclosan inhibition of mycobacterial inha in saccharomyces cerevisiae: yeast mitochondria as a novel platform for in vivo antimycolate assays.to demonstrate the suitability of yeast to act as a novel biotechnological platform for conducting in vivo inhibition assays using drugs with low efficacies towards their mycobacterial targets, such as occurs in the situation with triclosan and inha.201020158608
chemical inhibition of caax protease activity disrupts yeast ras localization.proteins possessing a c-terminal caax motif, such as the ras gtpases, undergo extensive post-translational modification that includes attachment of an isoprenoid lipid, proteolytic processing and carboxylmethylation. inhibition of the enzymes involved in these processes is considered a cancer-therapeutic strategy. we previously identified nine in vitro inhibitors of the yeast caax protease rce1p in a chemical library screen (manandhar et al., 2007). here, we demonstrate that these agents disrupt ...201020162532
active site remodelling accompanies thioester bond formation in the sumo e1.e1 enzymes activate ubiquitin (ub) and ubiquitin-like (ubl) proteins in two steps by carboxy-terminal adenylation and thioester bond formation to a conserved catalytic cysteine in the e1 cys domain. the structural basis for these intermediates remains unknown. here we report crystal structures for human sumo e1 in complex with sumo adenylate and tetrahedral intermediate analogues at 2.45 and 2.6 a, respectively. these structures show that side chain contacts to atp.mg are released after adenylat ...201020164921
evolution and regulation of cellular periodic processes: a role for paralogues.several cyclic processes take place within a single organism. for example, the cell cycle is coordinated with the 24 h diurnal rhythm in animals and plants, and with the 40 min ultradian rhythm in budding yeast. to examine the evolution of periodic gene expression during these processes, we performed the first systematic comparison in three organisms (homo sapiens, arabidopsis thaliana and saccharomyces cerevisiae) by using public microarray data. we observed that although diurnal-regulated and ...201020168326
expression of functional mammal flavocytochrome b(558) in yeast: comparison with improved insect cell system.activity of phagocyte nadph-oxidase relies on the assembly of five proteins, among them the transmembrane flavocytochrome b(558) (cytb(558)) which consists of a heterodimer of the gp91(phox) and p22(phox) subunits. the cytb(558) is the catalytic core of the nadph-oxidase that generates a superoxide anion from oxygen by using a reducing equivalent provided by nadph via fad and two hemes. we report a novel strategy to engineer and produce the stable and functional recombinant cytb(558) (rcytb(558) ...201020171157
cloning the human vitamin d receptor into the ptwin-1 expression vector.many of the actions of 1alpha,25-dihydroxyvitamin d3 [1,25(oh)2d3] are mediated by binding to the nuclear vitamin d receptor (vdr). vdr is a member of a superfamily of nuclear receptors that are ligand-dependent transcription factors. ligand binding induces conformational changes in the vdr that enable the receptor to interact with other coactivators to modulate gene transcription. in order to better characterize the binding of the vdr to 1,25(oh)2d3 and to analogs of 1,25(oh)2d3, we have cloned ...201020171280
anaplasma phagocytophilum ats-1 is imported into host cell mitochondria and interferes with apoptosis induction.anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, infects human neutrophils and inhibits mitochondria-mediated apoptosis. bacterial factors involved in this process are unknown. in the present study, we screened a genomic dna library of a. phagocytophilum for effectors of the type iv secretion system by a bacterial two-hybrid system, using a. phagocytophilum vird4 as bait. a hypothetical protein was identified as a putative effector, hereby named anaplasmatranslo ...201020174550
function and metabolism of sirtuin metabolite o-acetyl-adp-ribose.sirtuins catalyze the nad(+)-dependent deacetylation of target proteins, which are regulated by this reversible lysine modification. during deacetylation, the glycosidic bond of the nicotinamide ribose is cleaved to yield nicotinamide and the ribose accepts the acetyl group from substrate to produce o-acetyl-adp-ribose (oaadpr), which exists as an approximately 50:50 mixture of 2' and 3' isomers at neutral ph. discovery of this metabolite has fueled the idea that oaadpr may play an important rol ...201020176146
the nizp1 krab and c2hr domains cross-talk for transcriptional regulation.the nsd1 histone methyltransferase is involved in the outgrowth disorders sotos and weaver syndromes and childhood acute myeloid leukemia. nsd1 is a bona fida transcriptional co-repressor for nizp1 which is a protein including scan, krab, c2hr and zinc-finger domains. in this study the nizp1 krab-domain was identified to possess an intrinsic transcriptional activation capacity suppressed in cis by the presence of the c2hr domain. oppositely, the krab-domain supported c2hr domain mediated transcr ...201020176155
replication fork arrest and rdna silencing are two independent and separable functions of the replication terminator protein fob1 of saccharomyces cerevisiae.the replication terminator protein fob1 of saccharomyces cerevisiae is multifunctional, and it not only promotes polar replication fork arrest at the tandem ter sites located in the intergenic spacer region of rdna but also loads the nad-dependent histone deacetylase sir2 at ter sites via a protein complex called rent (regulator of nucleolar silencing and telophase exit). sir2 is a component of the rent complex, and its loading not only silences intrachromatid recombination in rdna but also rna ...201020179323
immunogenic yeast-based fermentate for cold/flu-like symptoms in nonvaccinated individuals.the common cold has a profound impact on employee attendance and productivity. seasonal influenza is responsible for approximately 200,000 hospitalizations and 36,000 deaths per year in the united states alone. over-the-counter medication efficacy has been questioned, and seasonal vaccination compliance issues abound. our previously reported randomized trial of an oral fermentation product found an adjuvant benefit for vaccinated individuals in terms of a significantly reduced incidence and dura ...201020180695
taf1 differentially enhances androgen receptor transcriptional activity via its n-terminal kinase and ubiquitin-activating and -conjugating domains.aberrant expression of androgen receptor (ar) coregulators has been linked to progression of prostate cancers to castration resistance. using the repressed transactivator yeast two-hybrid system, we found that tata binding protein-associated factor 1 (taf1) interacted with the ar. in tissue microarrays, taf1 was shown to steadily increase with duration of neoadjuvant androgen withdrawal and with progression to castration resistance. glutathione s-transferase pulldown assays established that taf1 ...201020181722
tom1l is involved in a novel signaling pathway important for the il-2 production in jurkat t cells stimulated by cd3/cd28 co-ligation.tom1l (target of myb-1 like) was identified as a binding partner for the full length and catalytically-active lck in a yeast 2-hybrid screening assay. here we show that in jurkat t cells stimulated by cd3/cd28 coligation where the expression of tom1l is reduced by lenti virus mediated-sirna results in a dramatically lower il-2 production. the production of il-2 in sirna treated cells stimulated with pma/ionomycin was not affected indicating an involvement of tom1l in a pathway proximal of tcr an ...201020182632
inferring genetic interactions via a nonlinear model and an optimization algorithm.biochemical pathways are gradually becoming recognized as central to complex human diseases and recently genetic/transcriptional interactions have been shown to be able to predict partial pathways. with the abundant information made available by microarray gene expression data (mged), nonlinear modeling of these interactions is now feasible. two of the latest advances in nonlinear modeling used sigmoid models to depict transcriptional interaction of a transcription factor (tf) for a target gene, ...201020184777
assembly and oligomerization of human atp synthase lacking mitochondrial subunits a and a6l.here we study atp synthase from human rho0 (rho zero) cells by clear native electrophoresis (cne or cn-page) and show that atp synthase is almost fully assembled in spite of the absence of subunits a and a6l. this identifies subunits a and a6l as two of the last subunits to complete the atp synthase assembly. minor amounts of dimeric and even tetrameric forms of the large assembly intermediate were preserved under the conditions of cne, suggesting that it associated further into higher order str ...201020188060
a trk/hkt-type k+ transporter from trypanosoma brucei.the molecular mechanisms of k(+) homeostasis are only poorly understood for protozoan parasites. trypanosoma brucei subsp. parasites, the causative agents of human sleeping sickness and nagana, are strictly extracellular and need to actively concentrate k(+) from their hosts' body fluids. the t. brucei genome contains two putative k(+) channel genes, yet the trypanosomes are insensitive to k(+) antagonists and k(+) channel-blocking agents, and they do not spontaneously depolarize in response to ...201020190075
glucuronide production by whole-cell biotransformation using genetically engineered fission yeast schizosaccharomyces pombe.drug metabolites generated by udp glycosyltransferases (ugts) are needed for drug development and toxicity studies, especially in the context of safety testing of metabolites during drug development. because chemical metabolite synthesis can be arduous, various biological approaches have been developed; however, no whole-cell biotransformation with recombinant microbes that express human ugts was yet achieved. in this study we expressed human udp glucose-6-dehydrogenase together with several hum ...201020008039
factor h and factor h-related protein 1 bind to human neutrophils via complement receptor 3, mediate attachment to candida albicans, and enhance neutrophil antimicrobial activity.the host complement system plays an important role in protection against infections. several human-pathogenic microbes were shown to acquire host complement regulators, such as factor h (cfh), that downregulate complement activation at the microbial surface and protect the pathogens from the opsonic and lytic effects of complement. because cfh can also bind to host cells, we addressed the role of cfh and cfh-related proteins as adhesion ligands in host-pathogen interactions. we show that the cfh ...201020008295
nix is a selective autophagy receptor for mitochondrial clearance.autophagy is the cellular homeostatic pathway that delivers large cytosolic materials for degradation in the lysosome. recent evidence indicates that autophagy mediates selective removal of protein aggregates, organelles and microbes in cells. yet, the specificity in targeting a particular substrate to the autophagy pathway remains poorly understood. here, we show that the mitochondrial protein nix is a selective autophagy receptor by binding to lc3/gabarap proteins, ubiquitin-like modifiers tha ...201020010802
alternative splicing and gene polymorphism of the human tap3/sec14l4 gene.three closely related human sec14p-like proteins (htap1, htap2, htap3, or sec14l2, sec14l3, sec14l4, respectively) have been described that are related to the saccharomyces cerevisiae sec14 protein. these proteins may participate in intracellular lipid transport and influence regulatory lipid-dependent events. here we report the isolation of an alternatively spliced htap3 cdna and a polymorphism within the coding region of the htap3/sec14l4 gene.201020012369
function of topbp1 in genome stability.human dna topoisomerase iibeta-binding protein 1 (topbp1) and its orthologues in other organisms are proteins consisting of multiple brct modules that have acquired several functions during evolution. these proteins execute their tasks by interacting with a great variety of proteins involved in nuclear processes. topbp1 is an essential protein that has numerous roles in the maintenance of the genomic integrity. in particular, it is required for the activation of atm and rad3-related (atr), a vit ...201020012580
ire1alpha controls cyclin a1 expression and promotes cell proliferation through xbp-1.ire1 is a conserved dual endoribonuclease/protein kinase that is indispensable for directing the endoplasmic reticulum (er) stress response in yeast, flies, and worms. in mammalian systems, however, the precise biological activities carried out by ire1alpha are unclear. here, molecular and chemical genetic approaches were used to control ire1 activity in a number of prostate cancer cell lines and the resulting impact on gene transcription, cell survival, and proliferation was examined. modulatin ...201020013084
identification and characterization of the type 2c protein phosphatase ptc4p in the human fungal pathogen candida albicans.type 2c protein phosphatases (pp2c) are monomeric enzymes and their activities require the presence of magnesium or manganese ions. there are seven pp2c genes, named from ptc1 to ptc7, in saccharomyces cerevisiae. in the current study we identified the captc4 gene in candida albicans and demonstrated that the captc4p protein is a typical pp2c enzyme, which is highly conserved in fungal species. deletion of captc4 renders candida cells sensitive to sodium and potassium ions as well as to antifung ...201020014041
apolipoprotein e interacts with hepatitis c virus nonstructural protein 5a and determines assembly of infectious particles.chronic hepatitis c virus (hcv) infection is a major cause of liver disease worldwide. restriction of hcv infection to human hepatocytes suggests that liver-specific host factors play a role in the viral life cycle. using a yeast-two-hybrid system, we identified apolipoprotein e (apoe) as a liver-derived host factor specifically interacting with hcv nonstructural protein 5a (ns5a) but not with other viral proteins. the relevance of apoe-ns5a interaction for viral infection was confirmed by co-im ...201020014138
from meiosis to postmeiotic events: uncovering the molecular roles of the meiosis-specific recombinase dmc1.in meiosis, the accurate segregation of maternal and paternal chromosomes is accomplished by homologous recombination. a central player in meiotic recombination is the dmc1 recombinase, a member of the reca/rad51 recombinase superfamily, which is widely conserved from viruses to humans. dmc1 is a meiosis-specific protein that functions with the ubiquitously expressed homolog, the rad51 recombinase, which is essential for both mitotic and meiotic recombination. since its discovery, it has been sp ...201020015079
gga autoinhibition revisited.the cytosolic adaptors gga1-3 mediate sorting of transmembrane proteins displaying a c-terminal acidic dileucine motif (dxxll) in their cytosolic domain. gga1 and gga3 contain similar but intrinsic motifs that are believed to serve as autoinhibitory sites activated by the phosphorylation of a serine positioned three residues upstream of the dxxll motif. in the present study, we have subjected the widely acknowledged concept of gga1 autoinhibition to a thorough structural and functional examinati ...201020015111
interaction between sdo1p and btn1p in the saccharomyces cerevisiae model for batten disease.juvenile batten disease is an autosomal recessive pediatric neurodegenerative disorder caused by mutations in the cln3 gene. the cln3 protein primarily resides in the lysosomal membrane, but its function is unknown. we demonstrate that cln3 interacts with sbds, the protein mutated in shwachman-bodian-diamond syndrome patients. we demonstrate that this protein-protein interaction is conserved between btn1p and sdo1p, the respective yeast saccharomyces cerevisiae orthologs of cln3 and sbds. it was ...201020015955
haspin: a newly discovered regulator of mitotic chromosome behavior.the haspins are divergent members of the eukaryotic protein kinase family that are conserved in many eukaryotic lineages including animals, fungi, and plants. recently-solved crystal structures confirm that the kinase domain of human haspin has unusual structural features that stabilize a catalytically active conformation and create a distinctive substrate binding site. haspin localizes predominantly to chromosomes and phosphorylates histone h3 at threonine-3 during mitosis, particularly at inne ...201019997740
the life span-prolonging effect of sirtuin-1 is mediated by autophagy.the life span of various model organisms can be extended by caloric restriction as well as by autophagy-inducing pharmacological agents. life span-prolonging effects have also been observed in yeast cells, nematodes and flies upon the overexpression of the deacetylase sirtuin-1. intrigued by these observations and by the established link between caloric restriction and sirtuin-1 activation, we decided to investigate the putative implication of sirtuin-1 in the response of human cancer cells and ...201020023410
modulation of plagl2 transactivation by positive cofactor 2 (pc2), a component of the arc/mediator complex.the pleomorphic adenoma gene (plag) family of transcription factors regulates a wide range of physiological processes, including cell proliferation, tissue-specific gene regulation, and embryonic development, although little is known regarding the mechanisms that regulate plag protein activity. in this study, a yeast two-hybrid screen identified pc2, a component of the mediator complex, as a plagl2-binding protein. we show that pc2 cooperates with plagl2 and pu.1 to enhance the activity of a kno ...201020025940
cryo-electron tomography of microtubule-kinesin motor complexes.microtubules complexed with molecular motors of the kinesin family or non-motor microtubule associated proteins (maps) such as tau or eb1 have been the subject of cryo-electron microcopy based 3-d studies for several years. most of these studies that targeted complexes with intact microtubules have been carried out by helical 3-d reconstruction, while few were analyzed by single particle approaches or from 2-d crystalline arrays. helical reconstruction of microtubule-map or motor complexes has b ...201020025975
nuclear targeting of a bacterial integrase that mediates site-specific recombination between bacterial and human target sequences.trwc is a bacterial protein involved in conjugative transfer of plasmid r388. it is transferred together with the dna strand into the recipient bacterial cell, where it can integrate the conjugatively transferred dna strand into its target sequence present in the recipient cell. considering that bacterial conjugation can occur between bacteria and eukaryotic cells, this protein has great biotechnological potential as a site-specific integrase. we have searched for possible trwc target sequences ...201021037296
a novel mammalian complex containing sin3b mitigates histone acetylation and rna polymerase ii progression within transcribed loci.transcription requires the progression of rna polymerase ii (rnap ii) through a permissive chromatin structure. recent studies of saccharomyces cerevisiae have demonstrated that the yeast sin3 protein contributes to the restoration of the repressed chromatin structure at actively transcribed loci. yet, the mechanisms underlying the restoration of the repressive chromatin structure at transcribed loci and its significance in gene expression have not been investigated in mammals. we report here th ...201021041482
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