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 recruits a specific histone H2A ubiquitin ligase, 2A-HUB/hRUL138, to a subset of regulated gene promoters. 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation. We suggest that distinct H2A ubiquitinases, each recruited based on interactions with different corepressor complexes, contribute to distinct transcriptional repression programs.

journal_name

Mol Cell

journal_title

Molecular cell

authors

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

doi

10.1016/j.molcel.2007.11.002

subject

Has Abstract

pub_date

2008-01-18 00:00:00

pages

69-80

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(07)00734-4

journal_volume

29

pub_type

杂志文章
  • Structural determinants of integrin recognition by talin.

    abstract::The binding of cytoplasmic proteins, such as talin, to the cytoplasmic domains of integrin adhesion receptors mediates bidirectional signal transduction. Here we report the crystal structure of the principal integrin binding and activating fragment of talin, alone and in complex with fragments of the beta 3 integrin t...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(02)00823-7

    authors: García-Alvarez B,de Pereda JM,Calderwood DA,Ulmer TS,Critchley D,Campbell ID,Ginsberg MH,Liddington RC

    更新日期:2003-01-01 00:00:00

  • Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.

    abstract::Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like prote...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.12.030

    authors: Chen L,Willis SN,Wei A,Smith BJ,Fletcher JI,Hinds MG,Colman PM,Day CL,Adams JM,Huang DC

    更新日期:2005-02-04 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

    doi:10.1016/j.molcel.2019.01.040

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

    更新日期:2019-04-18 00:00:00

  • Resetting the site: redirecting integration of an insertion sequence in a predictable way.

    abstract::Target site choice is a complex and poorly understood aspect of DNA transposition despite its importance in rational transposon-mediated gene delivery. Though most transposons choose target sites essentially randomly or with some slight sequence or structural preferences, insertion sequence IS608 from Helicobacter pyl...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.05.017

    authors: Guynet C,Achard A,Hoang BT,Barabas O,Hickman AB,Dyda F,Chandler M

    更新日期:2009-06-12 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

    doi:10.1016/j.molcel.2015.02.017

    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

  • 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

    doi:10.1016/j.molcel.2015.02.008

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

    更新日期:2015-04-02 00:00:00

  • How Rho exerts its muscle on RNA.

    abstract::Rho factor in bacteria terminates transcription by using energy from ATP hydrolysis to forcefully dissociate the transcripts from RNA polymerase. used data from presteady-state ATPase kinetics to support a rational mechanistic model for Rho's action on RNA. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.molcel.2006.06.002

    authors: Richardson JP

    更新日期:2006-06-23 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

    doi:10.1016/j.molcel.2004.06.008

    authors: Julien E,Herr W

    更新日期:2004-06-18 00:00:00

  • Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway.

    abstract::Atg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7(NTD)) recruits a unique "flexible region" from Atg3 (Atg3(FR)). The struct...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2011.08.034

    authors: Taherbhoy AM,Tait SW,Kaiser SE,Williams AH,Deng A,Nourse A,Hammel M,Kurinov I,Rock CO,Green DR,Schulman BA

    更新日期:2011-11-04 00:00:00

  • NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function.

    abstract::Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). Despite important advances in our understanding of Notch signal transduction, the regulation of Notch functions in the nucleus remains unclear. Using immunoaffinity p...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.08.022

    authors: Yatim A,Benne C,Sobhian B,Laurent-Chabalier S,Deas O,Judde JG,Lelievre JD,Levy Y,Benkirane M

    更新日期:2012-11-09 00:00:00

  • E3-Independent Constitutive Monoubiquitination Complements Histone Methyltransferase Activity of SETDB1.

    abstract::Ubiquitination typically occurs through the sequential action of three enzymes catalyzing ubiquitin activation (E1), conjugation (E2), and ligation (E3) and regulates diverse eukaryotic cellular processes. Although monoubiquitination commonly confers nondegradative activities, mechanisms underlying its temporal and sp...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.04.022

    authors: Sun L,Fang J

    更新日期:2016-06-16 00:00:00

  • CDC16 controls initiation at chromosome replication origins.

    abstract::The Cdc28p cyclin-dependent kinase is thought to both catalyze the onset of DNA replication and prevent rereplication by blocking the reassembly of initiation complexes at replication origins. Budding yeast with mutations in the CDC16 gene represent an exception to this model, because they rereplicate DNA despite bein...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)80046-5

    authors: Heichman KA,Roberts JM

    更新日期:1998-02-01 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

  • Uncovering a region of heat shock protein 90 important for client binding in E. coli and chaperone function in yeast.

    abstract::The heat shock protein 90 (Hsp90) family of heat shock proteins is an abundantly expressed and highly conserved family of ATP-dependent molecular chaperones. Hsp90 facilitates remodeling and activation of hundreds of proteins. In this study, we developed a screen to identify Hsp90-defective mutants in E. coli. The mut...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2012.11.017

    authors: Genest O,Reidy M,Street TO,Hoskins JR,Camberg JL,Agard DA,Masison DC,Wickner S

    更新日期:2013-02-07 00:00:00

  • Liquid Active Zones for Controlling the Phases of Synaptic Transmission.

    abstract::Wu et al. (2019) establish that the active zone proteins RIM and RIM-BP undergo liquid-liquid phase separation to tether Ca2+ channels. This important finding sets a new framework to study assembly and function of the presynaptic nerve terminal. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2019.02.020

    authors: Emperador-Melero J,Kaeser PS

    更新日期:2019-03-07 00:00:00

  • pRB Takes an EZ Path to a Repetitive Task.

    abstract::Repetitive DNA elements are essential for genome function; in this issue of Molecular Cell, Ishak et al. (2016) describe a novel mechanism of epigenetic repression at these elements that requires pRB-dependent recruitment of EZH2. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.molcel.2016.11.035

    authors: Sanidas I,Dyson NJ

    更新日期:2016-12-15 00:00:00

  • A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity.

    abstract::FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(01)00353-7

    authors: Rocchi S,Picard F,Vamecq J,Gelman L,Potier N,Zeyer D,Dubuquoy L,Bac P,Champy MF,Plunket KD,Leesnitzer LM,Blanchard SG,Desreumaux P,Moras D,Renaud JP,Auwerx J

    更新日期:2001-10-01 00:00:00

  • SOD1 as a molecular switch for initiating the homeostatic ER stress response under zinc deficiency.

    abstract::Zinc is an essential trace element, and impaired zinc homeostasis is implicated in the pathogenesis of various human diseases. However, the mechanisms cells use to respond to zinc deficiency are poorly understood. We previously reported that amyotrophic lateral sclerosis (ALS)-linked pathogenic mutants of SOD1 cause c...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.08.038

    authors: Homma K,Fujisawa T,Tsuburaya N,Yamaguchi N,Kadowaki H,Takeda K,Nishitoh H,Matsuzawa A,Naguro I,Ichijo H

    更新日期:2013-10-10 00:00:00

  • Mechanism of membrane insertion of a multimeric beta-barrel protein: perfringolysin O creates a pore using ordered and coupled conformational changes.

    abstract::Perfringolysin O, a bacterial cytolytic toxin, forms unusually large pores in cholesterol-containing membranes by the spontaneous insertion of two of its four domains into the bilayer. By monitoring the kinetics of domain-specific conformational changes and pore formation using fluorescence spectroscopy, the temporal ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/s1097-2765(00)00119-2

    authors: Heuck AP,Hotze EM,Tweten RK,Johnson AE

    更新日期:2000-11-01 00:00:00

  • Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.

    abstract::Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its assoc...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.09.018

    authors: Austenaa LM,Barozzi I,Simonatto M,Masella S,Della Chiara G,Ghisletti S,Curina A,de Wit E,Bouwman BA,de Pretis S,Piccolo V,Termanini A,Prosperini E,Pelizzola M,de Laat W,Natoli G

    更新日期:2015-11-05 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

    doi:10.1016/s1097-2765(03)00274-0

    authors: Smith KM,Yacobi R,Van Etten RA

    更新日期:2003-07-01 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

    doi:10.1016/s1097-2765(03)00405-2

    authors: Glover DM

    更新日期:2003-10-01 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

    doi:10.1016/j.molcel.2008.01.008

    authors: Apostolou E,Thanos D

    更新日期:2008-02-01 00:00:00

  • Bidirectional Transcription Arises from Two Distinct Hubs of Transcription Factor Binding and Active Chromatin.

    abstract::Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2015.04.006

    authors: Scruggs BS,Gilchrist DA,Nechaev S,Muse GW,Burkholder A,Fargo DC,Adelman K

    更新日期:2015-06-18 00:00:00

  • RhoA GTPase regulates B cell receptor signaling.

    abstract::The RhoA GTPase controls many cellular functions, including gene transcription and actin polymerization. Several lines of evidence suggest that Rho GTPases are required for B cell receptor (BCR) signaling, but whether RhoA is necessary has not been investigated. Here, we show that RhoA is activated, downstream of PI3K...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2004.12.012

    authors: Saci A,Carpenter CL

    更新日期:2005-01-21 00:00:00

  • A core complex of CPSF73, CPSF100, and Symplekin may form two different cleavage factors for processing of poly(A) and histone mRNAs.

    abstract::Metazoan histone mRNAs are unique: their pre-mRNAs contain no introns, and the mRNAs are not polyadenylated, ending instead in a conserved stem-loop structure. In Drosophila, canonical poly(A) signals are located downstream of the normal cleavage site of each histone gene and are utilized when histone 3' end formation...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2009.04.024

    authors: Sullivan KD,Steiniger M,Marzluff WF

    更新日期:2009-05-15 00:00:00

  • Magic Acts with the Cohesin Ring.

    abstract::Recent studies, including two in this issue of Molecular Cell (Elbatsh et al., 2016; Beckouët et al., 2016), cast light on how cohesin regulators harness the energy of ATP hydrolysis to open the cohesin ring and enable dynamic, regulated entrapment of chromosomes. ...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2016.02.003

    authors: Yu H

    更新日期:2016-02-18 00:00:00

  • Unweaving the meanings of messenger RNA sequences.

    abstract::In addition to protein-coding information, mRNAs harbor regulatory sequences necessary for appropriate processing of their precursors. Goren et al. (2006) and Wang et al. (2006) explore the diversity of these signals and the rules by which they function. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审

    doi:10.1016/j.molcel.2006.07.003

    authors: Guigó R,Valcárcel J

    更新日期:2006-07-21 00:00:00

  • Xist Deletional Analysis Reveals an Interdependency between Xist RNA and Polycomb Complexes for Spreading along the Inactive X.

    abstract::During X-inactivation, Xist RNA spreads along an entire chromosome to establish silencing. However, the mechanism and functional RNA elements involved in spreading remain undefined. By performing a comprehensive endogenous Xist deletion screen, we identify Repeat B as crucial for spreading Xist and maintaining Polycom...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2019.01.015

    authors: Colognori D,Sunwoo H,Kriz AJ,Wang CY,Lee JT

    更新日期:2019-04-04 00:00:00

  • Identification of a major determinant for serine-threonine kinase phosphoacceptor specificity.

    abstract::Eukaryotic protein kinases are generally classified as being either tyrosine or serine-threonine specific. Though not evident from inspection of their primary sequences, many serine-threonine kinases display a significant preference for serine or threonine as the phosphoacceptor residue. Here we show that a residue lo...

    journal_title:Molecular cell

    pub_type: 杂志文章

    doi:10.1016/j.molcel.2013.11.013

    authors: Chen C,Ha BH,Thévenin AF,Lou HJ,Zhang R,Yip KY,Peterson JR,Gerstein M,Kim PM,Filippakopoulos P,Knapp S,Boggon TJ,Turk BE

    更新日期:2014-01-09 00:00:00