Histone Ubiquitination: Triggering Gene Activity

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Molecular cell (Impact Factor: 14.02). 04/2008; 29(6):653-63. DOI: 10.1016/j.molcel.2008.02.014
Source: PubMed


Recently, many of the enzymes responsible for the addition and removal of ubiquitin from the histones H2A and H2B have been identified and characterized. From these studies, it has become clear that H2A and H2B ubiquitination play critical roles in regulating many processes within the nucleus, including transcription initiation and elongation, silencing, and DNA repair. In this review, we present the enzymes involved in H2A and H2B ubiquitination and discuss new evidence that links histone ubiquitination to other chromatin modifications, which has provided a model for the role of H2B ubiquitination, in particular, in transcription initiation and elongation.

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Available from: Jerry L Workman
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    • "Recent studies have suggested that the Mediator complex can facilitate transcriptional elongation (Donner et al, 2010; Takahashi et al, 2011; Galbraith et al, 2013; Wang et al, 2013b), and H2Bub plays a positive role in transcription elongation through an association with the PAF complex (Fig 3C) (Zhu et al, 2005; Tanny et al, 2007; Weake & Workman, 2008). Surprisingly, our study found that corporation of Mediator and PAF complexes can enhance RNF20/40- mediated H2B ubiquitination in vitro (Figs 3B and EV3), revealing interplays between Mediator, PAF complex, and RNF20/40 in regulating the ubiquitination level of H2B lysine 120 in transcription (Fig 8). "
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    ABSTRACT: The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23(-/-) (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation. © 2015 The Authors.
    Full-text · Article · Sep 2015 · The EMBO Journal
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    • "These observations suggest that H2Bub1 is a wellconserved cell biological event in higher eukaryotes. H2Bub1 is associated with the transcribed regions of highly expressed genes (Minsky et al., 2008) and could regulate transcription indirectly through trans-tail histone crosstalk with H3K4me2/H3K4me3, H3K79me3, and H3K36me2/H3K36me3 (Shilatifard, 2006; Weake and Workman, 2008; Berr et al., 2011; Braun and Madhani, 2012). In yeast, ubiquitination of H2B (Lys-123) mediated by Rad6 and Bre1 is a prerequisite for methylation of H3K4 and H3K79 (Robzyk et al., 2000; Sun and Allis, 2002; Hwang et al., 2003; Wood et al., 2003). "
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    ABSTRACT: Histone H2B monoubiquitination (H2Bub1) is an important regulatory mechanism in eukaryotic gene transcription and is essential for normal plant development. However, the function of H2Bub1 in reproductive development remains elusive. Here, we report OsHUB1 (Oryza sativa HISTONE MONO-UBIQUITINATION1) and OsHUB2, the homologues of Arabidopsis HUB1 and HUB2 proteins which function as E3 ligases in H2Bub1, are involved in late anther development in rice. oshub mutants exhibit abnormal tapetum development and aborted pollen in postmeiotic anthers. Knock-out of OsHUB1 or OsHUB2 results in the loss of H2Bub1, and a reduction in the levels of dimethylated lysine 4 on histone 3 (H3K4me2). Anther transcriptome analysis revealed that several key tapetum degradation-related genes including OsC4, OsCP1 and UDT1 were down-regulated in the mutants. Further, chromatin immunoprecipitation assays demonstrate that H2Bub1 directly targets OsC4, OsCP1 and UDT1 genes and enrichment of H2Bub1 and H3K4me2 in the targets is consistent to some degree. Our studies suggest that histone H2B monoubiquitination, mediated by OsHUB1 and OsHUB2, is an important epigenetic modification that in concert with H3K4me2 modulates transcriptional regulation of anther development in rice. Copyright © 2015, American Society of Plant Biologists.
    Full-text · Article · Jul 2015 · Plant physiology
    • "Instead, attachment of a single ubiquitin moiety significantly changes the histone mass and affects nucleosomal dynamics. The ubiquitin mark on H2B can also stimulate H3 K4 and K79 tri-methylation, thus coordinating 'cross-talks' between histone modifications, reviewed in [8]. We will discuss the functions of H2Aub in the first section and H2Bub in the second section. "
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    ABSTRACT: RNA Pol II elongation in eukaryotes is coupled with a series of histone modifications. Elongating RNA Pol II can be strongly stalled by lesions on the DNA template. However, it is unclear whether RNA Pol II stalling affects elongation-associated histone modifications. We have explored this important question by investigating the function of histone H2B mono-ubiquitylation (H2Bub), a well-characterized epigenetic mark associated with RNA Pol II elongation, in the cellular response to DNA lesions induced by ultraviolet (UV) radiation. We found that, in contrast to transcription elongation, RNA Pol II stalling induced by UV lesions triggers rapid and significant H2B deubiquitylation that removes ubiquitin from H2B. Interestingly, in yeast mutant cells that lack H2B deubiquitylation enzymes, rescue of the stalled RNA Pol II by transcription-coupled repair (TCR) is significantly impaired. Thus, our study has established a direct connection between RNA Pol II stalling and a histone modification response.
    No preview · Article · Feb 2015
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