Sir2 silences gene transcription by targeting the transition between RNA polymerase II initiation and elongation.

Abstract:

:It is well accepted that for transcriptional silencing in budding yeast, the evolutionarily conserved lysine deacetylase Sir2, in concert with its partner proteins Sir3 and Sir4, establishes a chromatin structure that prevents RNA polymerase II (Pol II) transcription. However, the mechanism of repression remains controversial. Here, we show that the recruitment of Pol II, as well as that of the general initiation factors TBP and TFIIH, occurs unimpeded to the silent HMRa1 and HMLalpha1/HMLalpha2 mating promoters. This, together with the fact that Pol II is Ser5 phosphorylated, implies that SIR-mediated silencing is permissive to both preinitiation complex (PIC) assembly and transcription initiation. In contrast, the occupancy of factors critical to both mRNA capping and Pol II elongation, including Cet1, Abd1, Spt5, Paf1C, and TFIIS, is virtually abolished. In agreement with this, efficiency of silencing correlates not with a restriction in Pol II promoter occupancy but with a restriction in capping enzyme recruitment. These observations pinpoint the transition between polymerase initiation and elongation as the step targeted by Sir2 and indicate that transcriptional silencing is achieved through the differential accessibility of initiation and capping/elongation factors to chromatin. We compare Sir2-mediated transcriptional silencing to a second repression mechanism, mediated by Tup1. In contrast to Sir2, Tup1 prevents TBP, Pol II, and TFIIH recruitment to the HMLalpha1 promoter, thereby abrogating PIC formation.

journal_name

Mol Cell Biol

authors

Gao L,Gross DS

doi

10.1128/MCB.00019-08

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

3979-94

issue

12

eissn

0270-7306

issn

1098-5549

pii

MCB.00019-08

journal_volume

28

pub_type

杂志文章
  • DNA bending by retinoid X receptor-containing retinoid and thyroid hormone receptor complexes.

    abstract::Retinoid X receptors (RXR) have been identified as common subunits in the regulation of multiple hormonal signaling pathways. Using circular permutation and phasing analysis of specific response elements, we present evidence that RXR-retinoic acid receptor and RXR-thyroid hormone receptor heterodimer or RXR-RXR homodi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.10.6509

    authors: Lu XP,Eberhardt NL,Pfahl M

    更新日期:1993-10-01 00:00:00

  • 14-3-3ε plays a role in cardiac ventricular compaction by regulating the cardiomyocyte cell cycle.

    abstract::Trabecular myocardium accounts for the majority of the ventricles during early cardiogenesis, but compact myocardium is the primary component at later developmental stages. Elucidation of the genes regulating compact myocardium development is essential to increase our understanding of left ventricular noncompaction (L...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00829-12

    authors: Kosaka Y,Cieslik KA,Li L,Lezin G,Maguire CT,Saijoh Y,Toyo-oka K,Gambello MJ,Vatta M,Wynshaw-Boris A,Baldini A,Yost HJ,Brunelli L

    更新日期:2012-12-01 00:00:00

  • Tissue localization of Drosophila melanogaster ras transcripts during development.

    abstract::Three ras homologs have been identified in Drosophila melanogaster. Here we describe the tissue distribution of their transcripts as analyzed by in situ hybridization. The RNAs of the three genes show a similar distribution at every developmental stage examined. In embryos, the transcripts are uniformly distributed. I...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.6.2241

    authors: Segal D,Shilo BZ

    更新日期:1986-06-01 00:00:00

  • Exon inclusion is dependent on predictable exonic splicing enhancers.

    abstract::We have previously formulated a list of approximately 2,000 RNA octamers as putative exonic splicing enhancers (PESEs) based on a statistical comparison of human exonic and nonexonic sequences (X. H. Zhang and L. A. Chasin, Genes Dev. 18:1241-1250, 2004). When inserted into a poorly spliced test exon, all eight tested...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.16.7323-7332.2005

    authors: Zhang XH,Kangsamaksin T,Chao MS,Banerjee JK,Chasin LA

    更新日期:2005-08-01 00:00:00

  • The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells.

    abstract::The transcriptional coactivator Cbp plays an important role in a wide range of cellular processes, including proliferation, differentiation, and apoptosis. Although studies have shown its requirement for hematopoietic stem cell (HSC) development, its role in adult HSC maintenance, as well as the cellular and molecular...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05830-11

    authors: Chan WI,Hannah RL,Dawson MA,Pridans C,Foster D,Joshi A,Göttgens B,Van Deursen JM,Huntly BJ

    更新日期:2011-12-01 00:00:00

  • Activation of an enhancer on the syndecan-1 gene is restricted to fibroblast growth factor family members in mesenchymal cells.

    abstract::Fibroblast growth factors (FGFs) induce a variety of biological effects on different cell types. They activate a number of genes, including immediate-early genes, such as the transcription factors Fos and Jun, which are also common targets for other tyrosine kinase receptor-activating growth factors. Here we describe ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.6.3210

    authors: Jaakkola P,Vihinen T,Määttä A,Jalkanen M

    更新日期:1997-06-01 00:00:00

  • Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated.

    abstract::HO endonuclease-induced double-strand breaks in Saccharomyces cerevisiae can undergo recombination by two distinct and competing pathways. In a plasmid containing a direct repeat, in which one repeat is interrupted by an HO endonuclease cut site, gap repair yields gene conversions while single-strand annealing produce...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.3.1292

    authors: Fishman-Lobell J,Rudin N,Haber JE

    更新日期:1992-03-01 00:00:00

  • Specific RNA residue interactions required for enzymatic functions of Tetrahymena telomerase.

    abstract::The ribonucleoprotein enzyme telomerase is a specialized reverse transcriptase that synthesizes telomeric DNA by copying a template sequence within the telomerase RNA. Here we analyze the actions of telomerase from Tetrahymena thermophila assembled in vivo with mutated or wild-type telomerase RNA to define further the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.1.66

    authors: Gilley D,Blackburn EH

    更新日期:1996-01-01 00:00:00

  • Dynamic Methylation of an L1 Transduction Family during Reprogramming and Neurodifferentiation.

    abstract::The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, a few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions in the early embryo, primordial germ line, and germ cells. L1 retrotransposition can also occur in the neurona...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00499-18

    authors: Salvador-Palomeque C,Sanchez-Luque FJ,Fortuna PRJ,Ewing AD,Wolvetang EJ,Richardson SR,Faulkner GJ

    更新日期:2019-03-19 00:00:00

  • An interaction between the DNA repair factor XPA and replication protein A appears essential for nucleotide excision repair.

    abstract::Replication protein A (RPA) is required for simian virus 40-directed DNA replication in vitro and for nucleotide excision repair (NER). Here we report that RPA and the human repair protein XPA specifically interact both in vitro and in vivo. Mapping of the RPA-interactive domains in XPA revealed that both of the large...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.10.5396

    authors: Li L,Lu X,Peterson CA,Legerski RJ

    更新日期:1995-10-01 00:00:00

  • Extrachromosomal replication of shuttle vectors in Dictyostelium discoideum.

    abstract::We cloned a 12.3-kilobase (kb) endogenous plasmid, Ddp1, found in several wild-type and laboratory strains of Dictyostelium discoideum into pBR322. The cloned plasmids have been used to cotransform D. discoideum cells with B10S, a transformation vector carrying a gene fusion conferring resistance to G418. Whereas B10S...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.11.3241

    authors: Firtel RA,Silan C,Ward TE,Howard P,Metz BA,Nellen W,Jacobson A

    更新日期:1985-11-01 00:00:00

  • Factors involved in specific transcription by mammalian RNA polymerase II: purification, genetic specificity, and TATA box-promoter interactions of TFIID.

    abstract::Selective and accurate transcription of purified genes by RNA polymerase II requires multiple factors. The factor designated TFIID was purified extensively from HeLa cell nuclear extracts by using a simple and novel complementation assay. Thus, TFIID was preferentially inactivated by mild heat treatment of a nuclear e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.10.4028

    authors: Nakajima N,Horikoshi M,Roeder RG

    更新日期:1988-10-01 00:00:00

  • Nuclear hormone receptors involved in neoplasia: erb A exhibits a novel DNA sequence specificity determined by amino acids outside of the zinc-finger domain.

    abstract::The erb A oncogene is a dominant negative allele of a thyroid hormone receptor gene and acts in the cancer cell by encoding a transcriptional repressor. We demonstrate here that the DNA sequence recognition properties of the oncogenic form of the erb A protein are significantly altered from those of the normal thyroid...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.4.2366

    authors: Chen H,Smit-McBride Z,Lewis S,Sharif M,Privalsky ML

    更新日期:1993-04-01 00:00:00

  • Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex.

    abstract::BCS1, a component of the inner membrane of mitochondria, belongs to the group of proteins with internal, noncleavable import signals. Import and intramitochondrial sorting of BCS1 are encoded in the N-terminal 126 amino acid residues. Three sequence elements were identified in this region, namely, the transmembrane do...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.7.2239-2250.2003

    authors: Stan T,Brix J,Schneider-Mergener J,Pfanner N,Neupert W,Rapaport D

    更新日期:2003-04-01 00:00:00

  • MdmX is required for p53 interaction with and full induction of the Mdm2 promoter after cellular stress.

    abstract::The activity of the tumor suppressor p53 is tightly controlled by its main negative regulator, Mdm2, which inhibits p53's transcriptional activity and targets it for degradation via the proteasome pathway. The closely related Mdm2 homolog, MdmX, is also considered to be a general inhibitor of transactivation by p53, t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06150-11

    authors: Biderman L,Poyurovsky MV,Assia Y,Manley JL,Prives C

    更新日期:2012-04-01 00:00:00

  • Characterization of a novel promoter insertion in the c-rel locus.

    abstract::Avian leukosis virus (ALV)-induced neoplasias are commonly found associated with integrations of proviral DNA in proximity to the myc gene. However, studies suggest that other genetic events are necessary for the complete neoplastic phenotype. A cell line (HP46) derived from an ALV-induced tumor has been analyzed and ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.9.4788

    authors: Kabrun N,Bumstead N,Hayman MJ,Enrietto PJ

    更新日期:1990-09-01 00:00:00

  • Combinatorial control of signal-induced exon repression by hnRNP L and PSF.

    abstract::Cells can regulate their protein repertoire in response to extracellular stimuli via alternative splicing; however, the mechanisms controlling this process are poorly understood. The CD45 gene undergoes alternative splicing in response to T-cell activation to regulate T-cell function. The ESS1 splicing silencer in CD4...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00419-07

    authors: Melton AA,Jackson J,Wang J,Lynch KW

    更新日期:2007-10-01 00:00:00

  • TRF1 controls telomere length and mitotic fidelity in epithelial homeostasis.

    abstract::TRF1 is a component of the shelterin complex at mammalian telomeres; however, a role for TRF1 in telomere biology in the context of the organism is unclear. In this study, we generated mice with transgenic TRF1 expression targeted to epithelial tissues (K5TRF1 mice). K5TRF1 mice have shorter telomeres in the epidermis...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01339-08

    authors: Muñoz P,Blanco R,de Carcer G,Schoeftner S,Benetti R,Flores JM,Malumbres M,Blasco MA

    更新日期:2009-03-01 00:00:00

  • Immunosuppression by N-methyl-D-aspartate receptor antagonists is mediated through inhibition of Kv1.3 and KCa3.1 channels in T cells.

    abstract::N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that play an important role in neuronal development, plasticity, and excitotoxicity. NMDAR antagonists are neuroprotective in animal models of neuronal diseases, and the NMDAR open-channel blocker memantine is used to treat Alzheimer's disease. In v...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01273-13

    authors: Kahlfuß S,Simma N,Mankiewicz J,Bose T,Lowinus T,Klein-Hessling S,Sprengel R,Schraven B,Heine M,Bommhardt U

    更新日期:2014-03-01 00:00:00

  • Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors.

    abstract::Transcriptional activation by nuclear hormone receptors is mediated by the 160-kDa family of nuclear receptor coactivators. These coactivators associate with DNA-bound nuclear receptors and transmit activating signals to the transcription machinery through two activation domains. In screening for mammalian proteins th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.5.1855-1867.2000

    authors: Huang SM,Stallcup MR

    更新日期:2000-03-01 00:00:00

  • Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.

    abstract::We constructed a series of recombinant genomes which directed expression of the enzyme chloramphenicol acetyltransferase (CAT) in mammalian cells. The prototype recombinant in this series, pSV2-cat, consisted of the beta-lactamase gene and origin of replication from pBR322 coupled to a simian virus 40 (SV40) early tra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.9.1044

    authors: Gorman CM,Moffat LF,Howard BH

    更新日期:1982-09-01 00:00:00

  • Regulatory role of MEF2D in serum induction of the c-jun promoter.

    abstract::Serum induction of c-jun expression in HeLa cells requires a MEF2 site at -59 in the c-jun promoter. MEF2 sites, found in many muscle-specific enhancers, are bound by a family of transcription factors, MEF2A through -D, which are related to serum response factor in their DNA binding domains. We have found that MEF2D i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.6.2907

    authors: Han TH,Prywes R

    更新日期:1995-06-01 00:00:00

  • Identification of estrogen receptor β as a SUMO-1 target reveals a novel phosphorylated sumoylation motif and regulation by glycogen synthase kinase 3β.

    abstract::SUMO conjugation has emerged as a dynamic process in regulating protein function. Here we identify estrogen receptor β (ERβ) to be a new target of SUMO-1. ERβ SUMO-1 modification occurs on a unique nonconsensus sumoylation motif which becomes fully competent upon phosphorylation of its contained serine residue, which ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06624-11

    authors: Picard N,Caron V,Bilodeau S,Sanchez M,Mascle X,Aubry M,Tremblay A

    更新日期:2012-07-01 00:00:00

  • p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes.

    abstract::Human cells lacking functional p53 exhibit a partial deficiency in nucleotide excision repair (NER), the pathway for repair of UV-induced DNA damage. The global genomic repair (GGR) subpathway of NER, but not transcription-coupled repair (TCR), is mainly affected by p53 loss or inactivation. We have utilized mouse emb...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.10.3705-3714.2000

    authors: Smith ML,Ford JM,Hollander MC,Bortnick RA,Amundson SA,Seo YR,Deng CX,Hanawalt PC,Fornace AJ Jr

    更新日期:2000-05-01 00:00:00

  • 2-Aminopurine selectively inhibits splicing of tumor necrosis factor alpha mRNA.

    abstract::2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.6.2814

    authors: Jarrous N,Osman F,Kaempfer R

    更新日期:1996-06-01 00:00:00

  • Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

    abstract::Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.4.1846

    authors: Riccio A,Pedone PV,Lund LR,Olesen T,Olsen HS,Andreasen PA

    更新日期:1992-04-01 00:00:00

  • Hepatitis C virus nonstructural 5B protein regulates tumor necrosis factor alpha signaling through effects on cellular IkappaB kinase.

    abstract::Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that possesses an RNA-dependent RNA polymerase activity. We recently reported that NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB and Jun N-terminal protein kinase (JNK). Since NS5A a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.8.3048-3059.2006

    authors: Choi SH,Park KJ,Ahn BY,Jung G,Lai MM,Hwang SB

    更新日期:2006-04-01 00:00:00

  • Association of type I phosphatidylinositol kinase activity with mutationally activated forms of human pp60c-src.

    abstract::Chicken embryo fibroblast cells overexpressing activated mutant forms of human pp60c-src, but not those overexpressing normal human pp60c-src, exhibited high levels of type I phosphatidylinositol (PI) kinase activity associated with pp60c-src. Levels of PI kinase activity were positively correlated with src tyrosine p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.3280

    authors: Chan TO,Tanaka A,Bjorge JD,Fujita DJ

    更新日期:1990-06-01 00:00:00

  • UBF binding in vivo is not restricted to regulatory sequences within the vertebrate ribosomal DNA repeat.

    abstract::The HMG box containing protein UBF binds to the promoter of vertebrate ribosomal repeats and is required for their transcription by RNA polymerase I in vitro. UBF can also bind in vitro to a variety of sequences found across the intergenic spacer in Xenopus and mammalian ribosomal DNA (rDNA) repeats. The high abundanc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.2.657-668.2002

    authors: O'Sullivan AC,Sullivan GJ,McStay B

    更新日期:2002-01-01 00:00:00

  • A conserved alpha-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.

    abstract::Sp1-like proteins are defined by three highly homologous C(2)H(2) zinc finger motifs that bind GC-rich sequences found in the promoters of a large number of genes essential for mammalian cell homeostasis. Here we report that TIEG2, a transforming growth factor beta-inducible Sp1-like protein with antiproliferative fun...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.15.5041-5049.2001

    authors: Zhang JS,Moncrieffe MC,Kaczynski J,Ellenrieder V,Prendergast FG,Urrutia R

    更新日期:2001-08-01 00:00:00