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 Celljournal_title
Molecular cellauthors
Zhou W,Zhu P,Wang J,Pascual G,Ohgi KA,Lozach J,Glass CK,Rosenfeld MGdoi
10.1016/j.molcel.2007.11.002subject
Has Abstractpub_date
2008-01-18 00:00:00pages
69-80issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(07)00734-4journal_volume
29pub_type
杂志文章相关文献
MOLECULAR CELL文献大全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
更新日期:2003-01-01 00:00:00
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
更新日期:2005-02-04 00:00:00
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
更新日期:2019-04-18 00:00:00
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
更新日期:2009-06-12 00:00:00
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
更新日期:2015-04-16 00:00:00
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
更新日期:2015-04-02 00:00:00
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
更新日期:2006-06-23 00:00:00
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
更新日期:2004-06-18 00:00:00
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
更新日期:2011-11-04 00:00:00
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
更新日期:2012-11-09 00:00:00
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
更新日期:2016-06-16 00:00:00
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
更新日期:1998-02-01 00:00:00
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
更新日期:2018-09-20 00:00:00
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
更新日期:2013-02-07 00:00:00
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
更新日期:2019-03-07 00:00:00
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
更新日期:2016-12-15 00:00:00
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
更新日期:2001-10-01 00:00:00
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
更新日期:2013-10-10 00:00:00
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
更新日期:2000-11-01 00:00:00
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
更新日期:2015-11-05 00:00:00
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
更新日期:2003-07-01 00:00:00
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
更新日期:2003-10-01 00:00:00
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
更新日期:2008-02-01 00:00:00
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
更新日期:2015-06-18 00:00:00
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
更新日期:2005-01-21 00:00:00
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
更新日期:2009-05-15 00:00:00
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
更新日期:2016-02-18 00:00:00
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
更新日期:2006-07-21 00:00:00
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
更新日期:2019-04-04 00:00:00
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
更新日期:2014-01-09 00:00:00