Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put.


:Chromatin modification by Polycomb proteins provides an essential strategy for gene silencing in higher eukaryotes. Polycomb repressive complexes (PRCs) silence key developmental regulators and are centrally integrated in the transcriptional circuitry of stem cells. PRC2 trimethylates histone H3 on lysine 27 (H3K27me3), and PRC1-type complexes ubiquitylate histone H2A and compact polynucleosomes. How PRCs are deployed to select and silence genomic targets is the subject of intense investigation. We review advances on targeting, modulation, and functions of PRC1 and PRC2 and progress on defining the transcriptional steps they impact. Recent findings emphasize PRC1 targeting independent of H3K27me3, nonenzymatic PRC1-mediated compaction, and connections between PRCs and noncoding RNAs. Systematic analyses of Polycomb complexes and associated histone modifications during DNA replication and mitosis have also emerged. The stage is now set to reveal fundamental epigenetic mechanisms that determine how Polycomb target genes are silenced and how Polycomb silence is preserved through cell-cycle progression.


Mol Cell


Molecular cell


Simon JA,Kingston RE




Has Abstract


2013-03-07 00:00:00














  • Plant PRRs and the activation of innate immune signaling.

    abstract::Despite being sessile organisms constantly exposed to potential pathogens and pests, plants are surprisingly resilient to infections. Plants can detect invaders via the recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). Plant PRRs are surface-localized receptor-like ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Macho AP,Zipfel C

    更新日期:2014-04-24 00:00:00

  • Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage.

    abstract::Posttranslational histone modifications play important roles in transcription and other chromatin-based processes. Compared to acetylation, methylation, and phosphorylation, very little is known about the function of histone ubiquitylation. Here, we report the purification and functional characterization of a histone ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wang H,Zhai L,Xu J,Joo HY,Jackson S,Erdjument-Bromage H,Tempst P,Xiong Y,Zhang Y

    更新日期:2006-05-05 00:00:00

  • MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence-Associated Secretory Phenotype.

    abstract::Oncogene-induced senescence (OIS) is a tumor-suppressive mechanism typified by stable proliferative arrest, a persistent DNA damage response, and the senescence-associated secretory phenotype (SASP), which helps to maintain the senescent state and triggers bystander senescence in a paracrine fashion. Here, we demonstr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Chen H,Ruiz PD,McKimpson WM,Novikov L,Kitsis RN,Gamble MJ

    更新日期:2015-09-03 00:00:00

  • Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.

    abstract::BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing s...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Chen J,Silver DP,Walpita D,Cantor SB,Gazdar AF,Tomlinson G,Couch FJ,Weber BL,Ashley T,Livingston DM,Scully R

    更新日期:1998-09-01 00:00:00

  • Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class.

    abstract::The guanidyl moiety is a component of fundamental metabolites, including the amino acid arginine, the energy carrier creatine, and the nucleobase guanine. Curiously, reports regarding the importance of free guanidine in biology are sparse, and no biological receptors that specifically recognize this compound have been...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Nelson JW,Atilho RM,Sherlock ME,Stockbridge RB,Breaker RR

    更新日期:2017-01-19 00:00:00

  • FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates.

    abstract::The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-termina...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Turco E,Witt M,Abert C,Bock-Bierbaum T,Su MY,Trapannone R,Sztacho M,Danieli A,Shi X,Zaffagnini G,Gamper A,Schuschnig M,Fracchiolla D,Bernklau D,Romanov J,Hartl M,Hurley JH,Daumke O,Martens S

    更新日期:2019-04-18 00:00:00

  • PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.

    abstract::Poly(ADP-ribose) polymerase-1 (PARP-1) creates the posttranslational modification PAR from substrate NAD(+) to regulate multiple cellular processes. DNA breaks sharply elevate PARP-1 catalytic activity to mount a cell survival repair response, whereas persistent PARP-1 hyperactivation during severe genotoxic stress is...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dawicki-McKenna JM,Langelier MF,DeNizio JE,Riccio AA,Cao CD,Karch KR,McCauley M,Steffen JD,Black BE,Pascal JM

    更新日期:2015-12-03 00:00:00

  • TOR-tured yeast find a new way to stand the heat.

    abstract::In this issue, Takahara and Maeda (2012) discover that together, Pbp1 and sequestration of the TORC1 complex in cytoplasmic mRNP stress granules provides a negative regulatory mechanism for TORC1 signaling during stress. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Buchan JR,Capaldi AP,Parker R

    更新日期:2012-07-27 00:00:00

  • Activation of a primed RING E3-E2-ubiquitin complex by non-covalent ubiquitin.

    abstract::RING ubiquitin ligases (E3) recruit ubiquitin-conjugate enzymes (E2) charged with ubiquitin (Ub) to catalyze ubiquitination. Non-covalent Ub binding to the backside of certain E2s promotes processive polyUb formation, but the mechanism remains elusive. Here, we show that backside bound Ub (Ub(B)) enhances both RING-in...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Buetow L,Gabrielsen M,Anthony NG,Dou H,Patel A,Aitkenhead H,Sibbet GJ,Smith BO,Huang DT

    更新日期:2015-04-16 00:00:00

  • Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1.

    abstract::Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Cha JH,Yang WH,Xia W,Wei Y,Chan LC,Lim SO,Li CW,Kim T,Chang SS,Lee HH,Hsu JL,Wang HL,Kuo CW,Chang WC,Hadad S,Purdie CA,McCoy AM,Cai S,Tu Y,Litton JK,Mittendorf EA,Moulder SL,Symmans WF,Thompson AM,Piwnica-

    更新日期:2018-08-16 00:00:00

  • Manipulation by Methylation: Garnishing mRNAs with m6Am.

    abstract::In two recent publications in Molecular Cell,Boulias et al. (2019) and Sendinc et al. (2019) use complementary approaches to map m6Am modification sites transcriptome-wide and demonstrate that m6Am can repress translation while increasing the stability of a subset of low-abundance transcripts. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Doxtader KA,Nam Y

    更新日期:2019-08-08 00:00:00

  • Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPR(mt).

    abstract::Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcrip...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Nargund AM,Fiorese CJ,Pellegrino MW,Deng P,Haynes CM

    更新日期:2015-04-02 00:00:00

  • MitoCPR: Meticulous Monitoring of Mitochondrial Proteostasis.

    abstract::Mitochondrial protein import stress compromises functioning of the organelles, due to inadequate supply of inner mitochondrial proteins. Weidberg and Amon (2018) describe a new monitoring pathway in budding yeast, which restores mitochondrial function following the clearing of accumulated unfolded pre-transported mito...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Desai R,Campanella M

    更新日期:2018-07-05 00:00:00

  • RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators.

    abstract::APOBEC1 is the catalytic component of an RNA editing complex but shows homology to activation-induced cytidine deaminase (AID), a protein whose function is to potentiate diversification of immunoglobulin gene DNA. Here, we show that APOBEC1 and its homologs APOBEC3C and APOBEC3G exhibit potent DNA mutator activity in ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Harris RS,Petersen-Mahrt SK,Neuberger MS

    更新日期:2002-11-01 00:00:00

  • The MRN-CtIP pathway is required for metaphase chromosome alignment.

    abstract::Faithful duplication of the genome in S phase followed by its accurate segregation in mitosis is essential to maintain genomic integrity. Recent studies have suggested that proteins involved in DNA transactions are also required for whole-chromosome stability. Here we demonstrate that the MRN (Mre11, Rad50, and Nbs1) ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Rozier L,Guo Y,Peterson S,Sato M,Baer R,Gautier J,Mao Y

    更新日期:2013-03-28 00:00:00

  • Chromosomal ARS1 has a single leading strand start site.

    abstract::Initiation sites for DNA synthesis in the chromosomal autonomously replicating sequence (ARS)1 of Saccharomyces cerevisiae were detected at the nucleotide level. The transition from discontinuous to continuous synthesis defines the origin of bidirectional replication (OBR), which mapped adjacent to the origin recognit...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bielinsky AK,Gerbi SA

    更新日期:1999-04-01 00:00:00

  • Identification of an mRNP complex regulating tumorigenesis at the translational elongation step.

    abstract::Transcript-selective translational regulation of epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) is directed by the hnRNP E1-containing TGF-β-activated-translational (BAT) mRNP complex. Herein, eukaryotic elongation factor-1 A1 (eEF1A1) is identified as an integral component of the BAT ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hussey GS,Chaudhury A,Dawson AE,Lindner DJ,Knudsen CR,Wilce MC,Merrick WC,Howe PH

    更新日期:2011-02-18 00:00:00

  • Trm9-catalyzed tRNA modifications link translation to the DNA damage response.

    abstract::Transcriptional and posttranslational signals are known mechanisms that promote efficient responses to DNA damage. We have identified Saccharomyces cerevisiae tRNA methyltransferase 9 (Trm9) as an enzyme that prevents cell death via translational enhancement of DNA damage response proteins. Trm9 methylates the uridine...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Begley U,Dyavaiah M,Patil A,Rooney JP,DiRenzo D,Young CM,Conklin DS,Zitomer RS,Begley TJ

    更新日期:2007-12-14 00:00:00

  • MicroRNA pathways modulate polyglutamine-induced neurodegeneration.

    abstract::Nine human neurodegenerative diseases are due to expansion of a CAG repeat- encoding glutamine within the open reading frame of the respective genes. Polyglutamine (polyQ) expansion confers dominant toxicity, resulting in neuronal degeneration. MicroRNAs (miRNAs) have been shown to modulate programmed cell death durin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bilen J,Liu N,Burnett BG,Pittman RN,Bonini NM

    更新日期:2006-10-06 00:00:00

  • Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC.

    abstract::Gene expression mediated by viral vectors is subject to cell-to-cell variability, which limits the accuracy of gene delivery. When coupled with single-cell measurements, however, such variability provides an efficient means to quantify signaling dynamics in mammalian cells. Here, we illustrate the utility of this appr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Wong JV,Yao G,Nevins JR,You L

    更新日期:2011-02-04 00:00:00

  • A role for the deep orange and carnation eye color genes in lysosomal delivery in Drosophila.

    abstract::Deep orange and carnation are two of the classic eye color genes in Drosophila. Here, we demonstrate that Deep orange is part of a protein complex that localizes to endosomal compartments. A second component of this complex is Carnation, a homolog of Sec1p-like regulators of membrane fusion. Because complete loss of d...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sevrioukov EA,He JP,Moghrabi N,Sunio A,Krämer H

    更新日期:1999-10-01 00:00:00

  • Yeast unravels epigenetic apoptosis control: deadly chat within a histone tail.

    abstract::An important paper by David Allis and colleagues (Ahn et al., 2006 [this issue of Molecular Cell]) describes a specific deacetylation/phosphorylation crosstalk at the histone H2B tail required for apoptosis induction in yeast, thus giving first insights into the poorly understood epigenetic regulation of cell death. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Carmona-Gutierrez D,Madeo F

    更新日期:2006-10-20 00:00:00

  • Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases.

    abstract::Cellular DNA damage causes stabilization and activation of the tumor suppressor and transcription factor p53, in part by promoting multiple covalent modifications of the p53 protein, including acetylation. We investigated the importance of acetylation in p53 function and the mechanism by which acetylation influences p...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Barlev NA,Liu L,Chehab NH,Mansfield K,Harris KG,Halazonetis TD,Berger SL

    更新日期:2001-12-01 00:00:00

  • Srs2 disassembles Rad51 filaments by a protein-protein interaction triggering ATP turnover and dissociation of Rad51 from DNA.

    abstract::Rad51 is a DNA recombinase functioning in the repair of DNA double-strand breaks and the generation of genetic diversity by homologous recombination (HR). In the presence of ATP, Rad51 self-assembles into an extended polymer on single-stranded DNA to catalyze strand exchange. Inappropriate HR causes genomic instabilit...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Antony E,Tomko EJ,Xiao Q,Krejci L,Lohman TM,Ellenberger T

    更新日期:2009-07-10 00:00:00

  • The heat shock response: life on the verge of death.

    abstract::Organisms must survive a variety of stressful conditions, including sudden temperature increases that damage important cellular structures and interfere with essential functions. In response to heat stress, cells activate an ancient signaling pathway leading to the transient expression of heat shock or heat stress pro...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Richter K,Haslbeck M,Buchner J

    更新日期:2010-10-22 00:00:00

  • A switch in mitotic histone H4 lysine 20 methylation status is linked to M phase defects upon loss of HCF-1.

    abstract::The abundant chromatin-associated human factor HCF-1 is a heterodimeric complex of HCF-1N and HCF-1C subunits that are essential for two stages of the cell cycle. The HCF-1N subunit promotes G1 phase progression, whereas the HCF-1C subunit ensures proper cytokinesis at completion of M phase. How the HCF-1C subunit fun...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Julien E,Herr W

    更新日期:2004-06-18 00:00:00

  • A bitter PP1 fights the sweet polo.

    abstract::In a recent paper in Developmental Cell, Yamashiro et al. (2008) report that the PP1 regulatory subunit MYPT1 interacts with PLK1 and antagonizes essential mitotic functions of PLK1, at least in part by promoting the dephosphorylation of PLK1 at Thr210. ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Archambault V,Chen F,Glover DM

    更新日期:2008-06-06 00:00:00

  • Identification of the TRiC/CCT substrate binding sites uncovers the function of subunit diversity in eukaryotic chaperonins.

    abstract::The ring-shaped hetero-oligomeric chaperonin TRiC/CCT uses ATP to fold a diverse subset of eukaryotic proteins. To define the basis of TRiC/CCT substrate recognition, we mapped the chaperonin interactions with the VHL tumor suppressor. VHL has two well-defined TRiC binding determinants. Each determinant contacts a spe...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Spiess C,Miller EJ,McClellan AJ,Frydman J

    更新日期:2006-10-06 00:00:00

  • HLTF's Ancient HIRAN Domain Binds 3' DNA Ends to Drive Replication Fork Reversal.

    abstract::Stalled replication forks are a critical problem for the cell because they can lead to complex genome rearrangements that underlie cell death and disease. Processes such as DNA damage tolerance and replication fork reversal protect stalled forks from these events. A central mediator of these DNA damage responses in hu...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kile AC,Chavez DA,Bacal J,Eldirany S,Korzhnev DM,Bezsonova I,Eichman BF,Cimprich KA

    更新日期:2015-06-18 00:00:00

  • A model for how ribosomal release factors induce peptidyl-tRNA cleavage in termination of protein synthesis.

    abstract::A major unresolved question in messenger RNA translation is how ribosomal release factors terminate protein synthesis. Class 1 release factors decode stop codons and trigger hydrolysis of the bond between the nascent polypeptide and tRNA some 75 A away from the decoding site. While the gross features of the release fa...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Trobro S,Aqvist J

    更新日期:2007-09-07 00:00:00