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














  • Lucifer's labyrinth--ten years of path finding in cell death.

    abstract::Cell death, as a foil to cell expansion, has become one of the most intensively studied research areas of modern biology. Almost every aspect of life is intimately enmeshed with the proper regulation of cell death, which either contributes to or forms the basis of most human disease pathogenesis. Now, with our ever-ex...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Meier P,Vousden KH

    更新日期:2007-12-14 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

  • Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation.

    abstract::Ubiquitin-mediated proteolysis regulates the activity of diverse receptor systems. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where i...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kavsak P,Rasmussen RK,Causing CG,Bonni S,Zhu H,Thomsen GH,Wrana JL

    更新日期:2000-12-01 00:00:00

  • Membrane Protein Dislocation by the Rhomboid Pseudoprotease Dfm1: No Pore Needed?

    abstract::Defective ER-resident membrane proteins need to be ejected into the cytoplasm in order to be degraded by the proteasome, but the exact mechanism remains unclear. In this issue of Molecular Cell, Neal et al. (2018) reveal that the rhomboid pseudoprotease Dfm1 defines the central ERAD component for membrane protein disl...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Avci D,Lemberg MK

    更新日期:2018-01-18 00:00:00

  • An In Vitro Assembly System Identifies Roles for RNA Nucleation and ATP in Yeast Stress Granule Formation.

    abstract::Stress granules (SGs) are condensates of mRNPs that form in response to stress. SGs arise by multivalent protein-protein, protein-RNA, and RNA-RNA interactions. However, the role of RNA-RNA interactions in SG assembly remains understudied. Here, we describe a yeast SG reconstitution system that faithfully recapitulate...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Begovich K,Wilhelm JE

    更新日期:2020-09-17 00:00:00

  • p53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis.

    abstract::The tumor suppressor p53 transcriptionally activates target genes to suppress cellular proliferation during stress. p53 has also been implicated in the repression of the proto-oncogene Myc, but the mechanism has remained unclear. Here, we identify Pvt1b, a p53-dependent isoform of the long noncoding RNA (lncRNA) Pvt1,...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Olivero CE,Martínez-Terroba E,Zimmer J,Liao C,Tesfaye E,Hooshdaran N,Schofield JA,Bendor J,Fang D,Simon MD,Zamudio JR,Dimitrova N

    更新日期:2020-02-20 00:00:00

  • Structural basis for interaction of the ribosome with the switch regions of GTP-bound elongation factors.

    abstract::Elongation factor G (EF-G) catalyzes tRNA translocation on the ribosome. Here a cryo-EM reconstruction of the 70S*EF-G ribosomal complex at 7.3 A resolution and the crystal structure of EF-G-2*GTP, an EF-G homolog, at 2.2 A resolution are presented. EF-G-2*GTP is structurally distinct from previous EF-G structures, an...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Connell SR,Takemoto C,Wilson DN,Wang H,Murayama K,Terada T,Shirouzu M,Rost M,Schüler M,Giesebrecht J,Dabrowski M,Mielke T,Fucini P,Yokoyama S,Spahn CM

    更新日期:2007-03-09 00:00:00

  • Emerging Principles of Gene Expression Programs and Their Regulation.

    abstract::Many mechanisms contribute to regulation of gene expression to ensure coordinated cellular behaviors and fate decisions. Transcriptional responses to external signals can consist of many hundreds of genes that can be parsed into different categories based on kinetics of induction, cell-type and signal specificity, and...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Pope SD,Medzhitov R

    更新日期:2018-08-02 00:00:00

  • Topography for independent binding of alpha-helical and PPII-helical ligands to a peroxisomal SH3 domain.

    abstract::While the function of most small signaling domains is confined to binary ligand interactions, the peroxisomal Pex13p SH3 domain has the unique capacity of binding to two different ligands, Pex5p and Pex14p. We have used this domain as a model to decipher its structurally independent ligand binding sites. By the combin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Douangamath A,Filipp FV,Klein AT,Barnett P,Zou P,Voorn-Brouwer T,Vega MC,Mayans OM,Sattler M,Distel B,Wilmanns M

    更新日期:2002-11-01 00:00:00

  • Arginine/serine-rich domains of SR proteins can function as activators of pre-mRNA splicing.

    abstract::Serine/arginine (SR)-rich splicing factors contain an RNA binding domain and an arginine/serine (RS)-rich domain required for protein-protein interactions. In addition to their roles in the basic splicing reaction, SR proteins function as components of splicing enhancer complexes. Here, we investigate the role of RS d...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Graveley BR,Maniatis T

    更新日期:1998-04-01 00:00:00

  • Molecular structures of crossover and noncrossover intermediates during gap repair in yeast: implications for recombination.

    abstract::The molecular structures of crossover (CO) and noncrossover (NCO) intermediates were determined by sequencing the products formed when a gapped plasmid was repaired using a diverged chromosomal template. Analyses were done in the absence of mismatch repair (MMR) to allow efficient detection of strand-transfer intermed...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Mitchel K,Zhang H,Welz-Voegele C,Jinks-Robertson S

    更新日期:2010-04-23 00:00:00

  • Growth factor withdrawal and apoptosis: the middle game.

    abstract::In this issue of Molecular Cell, detail molecular events that trigger apoptosis following growth factor withdrawal, linking irreversible mitochondrial permeabilization to activation of GSK-3 and subsequent phosphorylation, ubiquitinylation, and degradation of the antiapoptotic BCL-2 family member MCL-1. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Letai A

    更新日期:2006-03-17 00:00:00

  • Partners in Crime: Clandestine Operations among RAS-RAF Accomplices in Promoting Tumorigenesis.

    abstract::In this issue of Molecular Cell, Terrell et al. (2019) characterize the interactions of RAS-RAF complexes in live cells. Using bioluminescence resonance energy transfer (BRET) technology, they show that individual RAF family members exhibit distinct binding affinities to each RAS family protein, with CRAF exhibiting h...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Venkatanarayan A,Malek S

    更新日期:2019-12-19 00:00:00

  • Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation.

    abstract::Solving the biological roles of covalent histone modifications, including monoubiquitination of histone H2A, and the molecular mechanisms by which these modifications regulate specific transcriptional programs remains a central question for all eukaryotes. Here we report that the N-CoR/HDAC1/3 complex specifically rec...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Zhou W,Zhu P,Wang J,Pascual G,Ohgi KA,Lozach J,Glass CK,Rosenfeld MG

    更新日期:2008-01-18 00:00:00

  • Kin4 kinase delays mitotic exit in response to spindle alignment defects.

    abstract::For many polarized cells, it is critical that the mitotic spindle becomes positioned relative to the polarity axis. This is especially important in yeast, where the site of cytokinesis is predetermined. The spindle position checkpoint (SPOC) therefore delays mitotic exit of cells with a mispositioned spindle. One comp...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Pereira G,Schiebel E

    更新日期:2005-07-22 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

  • Yeast origins establish a strand bias for replicational mutagenesis.

    abstract::To determine whether replicational mutagenesis in the yeast genome is influenced by the positions of active origins, a reporter gene was placed in two orientations at multiple locations within a 39,000 bp region of chromosome III possessing two strong origins. The frequency of mutations resulting from misincorporation...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Pavlov YI,Newlon CS,Kunkel TA

    更新日期:2002-07-01 00:00:00

  • MLKL Requires the Inositol Phosphate Code to Execute Necroptosis.

    abstract::Necroptosis is an important form of lytic cell death triggered by injury and infection, but whether mixed lineage kinase domain-like (MLKL) is sufficient to execute this pathway is unknown. In a genetic selection for human cell mutants defective for MLKL-dependent necroptosis, we identified mutations in IPMK and ITPK1...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Dovey CM,Diep J,Clarke BP,Hale AT,McNamara DE,Guo H,Brown NW Jr,Cao JY,Grace CR,Gough PJ,Bertin J,Dixon SJ,Fiedler D,Mocarski ES,Kaiser WJ,Moldoveanu T,York JD,Carette JE

    更新日期:2018-06-07 00:00:00

  • Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination.

    abstract::How polycomb group proteins repress gene expression in vivo is not known. While histone-modifying activities of the polycomb repressive complexes (PRCs) have been studied extensively, in vitro data have suggested a direct activity of the PRC1 complex in compacting chromatin. Here, we investigate higher-order chromatin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Eskeland R,Leeb M,Grimes GR,Kress C,Boyle S,Sproul D,Gilbert N,Fan Y,Skoultchi AI,Wutz A,Bickmore WA

    更新日期:2010-05-14 00:00:00

  • Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt.

    abstract::Forkhead box O (FOXO) transcription factors, the key regulators of cell survival, are negatively controlled through the PI3K-Akt signaling pathway. Phosphorylation of FOXO by Akt leads to cytoplasmic localization and subsequent degradation via the ubiquitin-proteasome system. Here we show a paradigm of FOXO1 regulatio...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Yamagata K,Daitoku H,Takahashi Y,Namiki K,Hisatake K,Kako K,Mukai H,Kasuya Y,Fukamizu A

    更新日期:2008-10-24 00:00:00

  • Linking differential chromatin loops to transcriptional decisions.

    abstract::GATA-1 and GATA-2 control proliferation and differentiation of hematopoietic progenitor cells via transcriptional regulation. In this issue of Molecular Cell, Jing et al. (2008) demonstrate that GATA factor exchange on the Kit locus directs a transcriptional switch by reconfiguring chromatin loops. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Apostolou E,Thanos D

    更新日期:2008-02-01 00:00:00

  • Pif1-Family Helicases Support Fork Convergence during DNA Replication Termination in Eukaryotes.

    abstract::The convergence of two DNA replication forks creates unique problems during DNA replication termination. In E. coli and SV40, the release of torsional strain by type II topoisomerases is critical for converging replisomes to complete DNA synthesis, but the pathways that mediate fork convergence in eukaryotes are unkno...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Deegan TD,Baxter J,Ortiz Bazán MÁ,Yeeles JTP,Labib KPM

    更新日期:2019-04-18 00:00:00

  • Aurora A on the mitotic spindle is activated by the way it holds its partner.

    abstract::An exciting study in this issue reveals how binding of the microtubule associated protein TPX2 to the mitotic kinase Aurora A induces a conformational change. This moves the phosphorylated activation domain into a more compact position within the kinase core, providing a better substrate binding platform and hiding th...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Glover DM

    更新日期:2003-10-01 00:00:00

  • Propagating prions in fungi and mammals.

    abstract::Prions constitute a rare class of protein, which can switch to a robust amyloid form and then propagate that form in the absence of a nucleic acid determinant, thereby creating a unique, protein-only infectious agent. Details of the mechanism that drives conversion to the prion form and then subsequent propagation of ...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Tuite MF,Koloteva-Levin N

    更新日期:2004-06-04 00:00:00

  • Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone H3.

    abstract::In Saccharomyces cerevisiae, methylation of histone H3 at active genes is an epigenetic mark that distinguishes active from silent chromatin and functions as a short-term "memory" of recent transcription. Methylation of H3 at lysine residues K4 and K79 depends on ubiquitylation of histone H2B, but the mechanisms linki...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Ezhkova E,Tansey WP

    更新日期:2004-02-13 00:00:00

  • Histone acetylation by HBO1 tightens replication licensing.

    abstract::In this issue of Molecular Cell, Miotto and Struhl (2010) suggest that replication licensing, the loading of Mcm2-7 onto DNA, is promoted by HBO1 acetylating histone H4 at replication origins, providing a molecular view of how chromatin status influences origin usage. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Chadha GS,Blow JJ

    更新日期:2010-01-15 00:00:00

  • Autoinhibition of Bcr-Abl through its SH3 domain.

    abstract::Bcr-Abl is a dysregulated tyrosine kinase whose mechanism of activation is unclear. Here, we demonstrate that, like c-Abl, Bcr-Abl is negatively regulated through its SH3 domain. Kinase activity, transformation, and leukemogenesis by Bcr-Abl are greatly impaired by mutations of the Bcr coiled-coil domain that disrupt ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Smith KM,Yacobi R,Van Etten RA

    更新日期:2003-07-01 00:00:00

  • Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin.

    abstract::Multi-subunit SMC ATPases control chromosome superstructure and DNA topology, presumably by DNA translocation and loop extrusion. Chromosomal DNA is entrapped within the tripartite SMCkleisin ring. Juxtaposed SMC heads ("J heads") or engaged SMC heads ("E heads") split the SMCkleisin ring into "S" and "K" sub-compartm...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Vazquez Nunez R,Ruiz Avila LB,Gruber S

    更新日期:2019-07-25 00:00:00

  • Regulation of SUMOylation by reversible oxidation of SUMO conjugating enzymes.

    abstract::Posttranslational modification with small ubiquitin-related modifier (SUMO) has emerged as a central regulatory mechanism of protein function. However, little is known about the regulation of sumoylation itself. It has been reported that it is increased after exposure to various stresses including strong oxidative str...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Bossis G,Melchior F

    更新日期:2006-02-03 00:00:00

  • Unambiguous identification of miRNA:target site interactions by different types of ligation reactions.

    abstract::To exert regulatory function, miRNAs guide Argonaute (AGO) proteins to partially complementary sites on target RNAs. Crosslinking and immunoprecipitation (CLIP) assays are state-of-the-art to map AGO binding sites, but assigning the targeting miRNA to these sites relies on bioinformatics predictions and is therefore i...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Grosswendt S,Filipchyk A,Manzano M,Klironomos F,Schilling M,Herzog M,Gottwein E,Rajewsky N

    更新日期:2014-06-19 00:00:00