EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency.

Abstract:

:Trimethylation on H3K27 (H3K27me3) mediated by Polycomb repressive complex 2 (PRC2) has been linked to embryonic stem cell (ESC) identity and pluripotency. EZH2, the catalytic subunit of PRC2, has been reported as the sole histone methyltransferase that methylates H3K27 and mediates transcriptional silencing. Analysis of Ezh2(-/-) ESCs suggests existence of an additional enzyme(s) catalyzing H3K27 methylation. We have identified EZH1, a homolog of EZH2 that is physically present in a noncanonical PRC2 complex, as an H3K27 methyltransferase in vivo and in vitro. EZH1 colocalizes with the H3K27me3 mark on chromatin and preferentially preserves this mark on development-related genes in Ezh2(-/-) ESCs. Depletion of Ezh1 in cells lacking Ezh2 abolishes residual methylation on H3K27 and derepresses H3K27me3 target genes, demonstrating a role of EZH1 in safeguarding ESC identity. Ezh1 partially complements Ezh2 in executing pluripotency during ESC differentiation, suggesting that cell-fate transitions require epigenetic specificity.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Shen X,Liu Y,Hsu YJ,Fujiwara Y,Kim J,Mao X,Yuan GC,Orkin SH

doi

10.1016/j.molcel.2008.10.016

subject

Has Abstract

pub_date

2008-11-21 00:00:00

pages

491-502

issue

4

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(08)00732-6

journal_volume

32

pub_type

杂志文章
  • Frozen in Transcription: Cryo-EM Structures of Pol II Transcribing through a Nucleosome.

    abstract::In a recent publication in Science, Kujirai et al. (2018) use single-particle cryo-EM to resolve several Pol II-nucleosome interactions, shedding new light on transcription elongation in a native chromatin environment. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2018.11.027

    authors: Noe Gonzalez M,Conaway RC,Conaway JW

    更新日期:2018-12-06 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

    doi:10.1016/j.molcel.2009.12.028

    authors: Chadha GS,Blow JJ

    更新日期:2010-01-15 00:00:00

  • Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ.

    abstract::Adrenergic stimulation of the heart engages cAMP and phosphoinositide second messenger signaling cascades. Cardiac phosphoinositide 3-kinase p110γ participates in these processes by sustaining β-adrenergic receptor internalization through its catalytic function and by controlling phosphodiesterase 3B (PDE3B) activity ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.01.030

    authors: Perino A,Ghigo A,Ferrero E,Morello F,Santulli G,Baillie GS,Damilano F,Dunlop AJ,Pawson C,Walser R,Levi R,Altruda F,Silengo L,Langeberg LK,Neubauer G,Heymans S,Lembo G,Wymann MP,Wetzker R,Houslay MD,Iaccarino G,S

    更新日期:2011-04-08 00:00:00

  • A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends.

    abstract::The mechanisms by which telomeres are distinguished from DNA double-strand breaks are poorly understood. Here we have defined the minimal requirements for the protection of telomeric DNA ends from nonhomologous end-joining (NHEJ). Neither long, single-stranded overhangs nor t loop formation is essential to prevent NHE...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2007.03.023

    authors: Bae NS,Baumann P

    更新日期:2007-05-11 00:00:00

  • Controlling the elongation phase of transcription with P-TEFb.

    abstract::The positive transcription elongation factor b (P-TEFb) is a cyclin-dependent kinase that controls the elongation phase of transcription by RNA polymerase II (RNAPII). This process is made possible by the reversal of effects of negative elongation factors that include NELF and DSIF. In complex organisms, elongation co...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2006.06.014

    authors: Peterlin BM,Price DH

    更新日期:2006-08-04 00:00:00

  • A BLAST from the past: ancient origin of human Sm proteins.

    abstract::In this issue of Molecular Cell, Zhang et al. and Møller et al. independently report studies of the E. coli Hfq protein, revealing significant sequence similarities with human Sm proteins. Their findings suggest that Hfq, and the Sm and Sm-like (Lsm) proteins, may function in stabilizing interactions between RNA molec...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/s1097-2765(02)00429-x

    authors: Donahue WF,Jarrell KA

    更新日期:2002-01-01 00:00:00

  • Dynamics of enhancer-promoter communication during differentiation-induced gene activation.

    abstract::We analyzed the order of recruitment of factors to the HNF-4alpha regulatory regions upon the initial activation of the gene during enterocyte differentiation. An initially independent assembly of regulatory complexes at the proximal promoter and the upstream enhancer regions was followed by the tracking of the entire...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00786-4

    authors: Hatzis P,Talianidis I

    更新日期:2002-12-01 00:00:00

  • β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

    abstract::β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which signi...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.07.036

    authors: Han YM,Bedarida T,Ding Y,Somba BK,Lu Q,Wang Q,Song P,Zou MH

    更新日期:2018-09-20 00:00:00

  • A branched pathway governing the activation of a developmental transcription factor by regulated intramembrane proteolysis.

    abstract::The proteolytic activation of the membrane-associated transcription factor pro-sigma(K) is controlled by a signal transduction pathway during sporulation in the bacterium Bacillus subtilis. The pro-sigma(K) processing enzyme SpoIVFB, a membrane-embedded metalloprotease, is held inactive by two other integral-membrane ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.05.019

    authors: Campo N,Rudner DZ

    更新日期:2006-07-07 00:00:00

  • Caspase-mediated cleavage, IAP binding, and ubiquitination: linking three mechanisms crucial for Drosophila NF-kappaB signaling.

    abstract::Innate immune responses are critical for the immediate protection against microbial infection. In Drosophila, infection leads to the rapid and robust production of antimicrobial peptides through two NF-kappaB signaling pathways-IMD and Toll. The IMD pathway is triggered by DAP-type peptidoglycan, common to most Gram-n...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.12.036

    authors: Paquette N,Broemer M,Aggarwal K,Chen L,Husson M,Ertürk-Hasdemir D,Reichhart JM,Meier P,Silverman N

    更新日期:2010-01-29 00:00:00

  • ZFAND1 Recruits p97 and the 26S Proteasome to Promote the Clearance of Arsenite-Induced Stress Granules.

    abstract::Stress granules (SGs) are cytoplasmic assemblies of mRNPs stalled in translation initiation. They are induced by various stress conditions, including exposure to the environmental toxin and carcinogen arsenic. While perturbed SG turnover is linked to the pathogenesis of neurodegenerative diseases, the molecular mechan...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.04.021

    authors: Turakhiya A,Meyer SR,Marincola G,Böhm S,Vanselow JT,Schlosser A,Hofmann K,Buchberger A

    更新日期:2018-06-07 00:00:00

  • Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia coli.

    abstract::In bacteria, Hfq is a core RNA chaperone that catalyzes the interaction of mRNAs with regulatory small RNAs (sRNAs). To determine in vivo RNA sequence requirements for Hfq interactions, and to study riboregulation in a bacterial pathogen, Hfq was UV crosslinked to RNAs in enterohemorrhagic Escherichia coli (EHEC). Hfq...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.05.006

    authors: Tree JJ,Granneman S,McAteer SP,Tollervey D,Gally DL

    更新日期:2014-07-17 00:00:00

  • Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis.

    abstract::The double Holliday junction (dHJ) is generally regarded to be a key intermediate of meiotic recombination, whose resolution is critical for the formation of crossover recombinants. In fission yeast, the Mus81-Eme1 endonuclease has been implicated in resolving dHJs. Consistent with this role, we show that Mus81-Eme1 i...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00343-5

    authors: Osman F,Dixon J,Doe CL,Whitby MC

    更新日期:2003-09-01 00:00:00

  • Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 alternative splicing.

    abstract::Signal-induced alternative splicing of the CD45 gene in human T cells is essential for proper immune function. Skipping of the CD45 variable exons is controlled, in large part, by the recruitment of PSF to the pre-mRNA substrate upon T cell activation; however, the signaling cascade leading to exon exclusion has remai...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2010.09.013

    authors: Heyd F,Lynch KW

    更新日期:2010-10-08 00:00:00

  • WTX: an unexpected regulator for p53.

    abstract::The WTX gene is frequently lost or mutated in Wilms tumor. In this issue of Molecular Cell, Kim et al. (2012) identify WTX modulation of p53 tumor-suppressor activity through regulation of p53 acetylation. Therefore, WTX differentially regulates the oncogenic β-catenin pathway and the tumor-suppressing p53 pathway. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2012.02.010

    authors: Dai C,Gu W

    更新日期:2012-03-09 00:00:00

  • Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration.

    abstract::HIV-1 Nef plays important roles in HIV-1 replication and pathogenesis. It is translated from completely spliced HIV-1 RNA, and its expression is inherently regulated at the levels of viral DNA transcription and RNA splicing. Here we show that Sam68 cytoplasmic mutants potently suppress Nef expression. The suppression ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2008.11.024

    authors: Henao-Mejia J,Liu Y,Park IW,Zhang J,Sanford J,He JJ

    更新日期:2009-01-16 00:00:00

  • Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment.

    abstract::The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00283-0

    authors: Espinosa JM,Emerson BM

    更新日期:2001-07-01 00:00:00

  • Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.

    abstract::Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2014.12.039

    authors: Sahtoe DD,van Dijk WJ,El Oualid F,Ekkebus R,Ovaa H,Sixma TK

    更新日期:2015-03-05 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

    doi:10.1016/j.molcel.2006.03.035

    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

  • 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

    doi:10.1016/j.molcel.2009.05.026

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

    更新日期:2009-07-10 00:00:00

  • The little elongation complex functions at initiation and elongation phases of snRNA gene transcription.

    abstract::The small nuclear RNA (snRNA) genes have been widely used as a model system for understanding transcriptional regulation due to the unique aspects of their promoter structure, selectivity for either RNA polymerase (Pol) II or III, and because of their unique mechanism of termination that is tightly linked with the pro...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.07.003

    authors: Hu D,Smith ER,Garruss AS,Mohaghegh N,Varberg JM,Lin C,Jackson J,Gao X,Saraf A,Florens L,Washburn MP,Eissenberg JC,Shilatifard A

    更新日期:2013-08-22 00:00:00

  • A Dicer-Independent Route for Biogenesis of siRNAs that Direct DNA Methylation in Arabidopsis.

    abstract::DNA methylation directed by 24-nucleotide (nt) small interfering RNAs (siRNAs) plays critical roles in gene regulation and transposon silencing in Arabidopsis. 24-nt siRNAs are known to be processed from double-stranded RNAs by Dicer-like 3 (DCL3) and loaded into the effector Argonaute 4 (AGO4). Here we report a disti...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.11.015

    authors: Ye R,Chen Z,Lian B,Rowley MJ,Xia N,Chai J,Li Y,He XJ,Wierzbicki AT,Qi Y

    更新日期:2016-01-21 00:00:00

  • Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs.

    abstract::The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation, whereas FGF-10 pro...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.08.002

    authors: Francavilla C,Rigbolt KT,Emdal KB,Carraro G,Vernet E,Bekker-Jensen DB,Streicher W,Wikström M,Sundström M,Bellusci S,Cavallaro U,Blagoev B,Olsen JV

    更新日期:2013-09-26 00:00:00

  • The Biogenesis, Functions, and Challenges of Circular RNAs.

    abstract::Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal m...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审

    doi:10.1016/j.molcel.2018.06.034

    authors: Li X,Yang L,Chen LL

    更新日期:2018-08-02 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

    doi:10.1016/j.molcel.2014.03.049

    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

  • Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes.

    abstract::In order to determine the global effects of oncogenic Ras and Akt signaling pathways on translational efficiencies, we compared the gene expression profiles of total cellular mRNA and mRNA associated with polysomes. We found that the immediate effect of Ras and Akt signaling blockade on transcription was relatively mo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00395-2

    authors: Rajasekhar VK,Viale A,Socci ND,Wiedmann M,Hu X,Holland EC

    更新日期:2003-10-01 00:00:00

  • ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts.

    abstract::S(N)1-type alkylating agents that produce cytotoxic O(6)-methyl-G (O(6)-meG) DNA adducts induce cell cycle arrest and apoptosis in a manner requiring the DNA mismatch repair (MMR) proteins MutSalpha and MutLalpha. Here, we show that checkpoint signaling in response to DNA methylation occurs during S phase and requires...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2006.04.023

    authors: Yoshioka K,Yoshioka Y,Hsieh P

    更新日期:2006-05-19 00:00:00

  • Exon Junction Complexes Suppress Spurious Splice Sites to Safeguard Transcriptome Integrity.

    abstract::Productive splicing of human precursor messenger RNAs (pre-mRNAs) requires the correct selection of authentic splice sites (SS) from the large pool of potential SS. Although SS consensus sequence and splicing regulatory proteins are known to influence SS usage, the mechanisms ensuring the effective suppression of cryp...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2018.08.030

    authors: Boehm V,Britto-Borges T,Steckelberg AL,Singh KK,Gerbracht JV,Gueney E,Blazquez L,Altmüller J,Dieterich C,Gehring NH

    更新日期:2018-11-01 00:00:00

  • Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation.

    abstract::Protein kinase B/Akt plays crucial roles in promoting cell survival and mediating insulin responses. The enzyme is stimulated by phosphorylation at two regulatory sites: Thr 309 of the activation segment and Ser 474 of the hydrophobic motif, a conserved feature of many AGC kinases. Analysis of the crystal structures o...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00550-6

    authors: Yang J,Cron P,Thompson V,Good VM,Hess D,Hemmings BA,Barford D

    更新日期:2002-06-01 00:00:00

  • RNA polymerase II/TFIIF structure and conserved organization of the initiation complex.

    abstract::The structure of an RNA polymerase II/general transcription factor TFIIF complex was determined by cryo-electron microscopy and single particle analysis. Density due to TFIIF was not concentrated in one area but rather was widely distributed across the surface of the polymerase. The largest subunit of TFIIF interacted...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(03)00387-3

    authors: Chung WH,Craighead JL,Chang WH,Ezeokonkwo C,Bareket-Samish A,Kornberg RD,Asturias FJ

    更新日期:2003-10-01 00:00:00