H2B Ubiquitylation Plays a Role in Nucleosome Dynamics during Transcription Elongation

Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Molecular cell (Impact Factor: 14.02). 08/2008; 31(1):57-66. DOI: 10.1016/j.molcel.2008.04.025
Source: PubMed


The monoubiquitylation of histone H2B has been associated with transcription initiation and elongation, but its role in these processes is poorly understood. We report that H2B ubiquitylation is required for efficient reassembly of nucleosomes during RNA polymerase II (Pol II)-mediated transcription elongation in yeast. This role is carried out in cooperation with the histone chaperone Spt16, and in the absence of H2B ubiquitylation and functional Spt16, chromatin structure is not properly restored in the wake of elongating Pol II. Moreover, H2B ubiquitylation and Spt16 play a role in each other's regulation. H2B ubiquitylation is required for the stable accumulation of Spt16 at the GAL1 coding region, and Spt16 regulates the formation of ubiquitylated H2B both globally and at the GAL1 gene. These data provide a mechanism linking H2B ubiquitylation to Spt16 in the regulation of nucleosome dynamics during transcription elongation.

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    • "Taken together, these results strongly suggest interplays between Mediator, the PAF complex, and the H2B monoubiquitination machinery, and Mediator and PAF complexes may collaboratively promote H2B lysine 120 ubiquitination through RNF20/40 (Fig 8). MED23-dependent and MED23-independent H2Bub regulation and transcriptional activities Mono-ubiquitination of H2B enhances the accessibility of chromatin to transcriptional activators (Fierz et al, 2011) and facilitates FACTdependent Pol II stimulation (Pavri et al, 2006; Fleming et al, 2008). We therefore examined whether MED23 could control transcriptional activation through H2B mono-ubiquitination. "
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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.
    The EMBO Journal 09/2015; DOI:10.15252/embj.201591279 · 10.43 Impact Factor
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    • "First, this mark physically alters chromatin compaction and nucleosome stability (Fleming et al. 2008; Chandrasekharan et al. 2009; Fierz et al. 2011). Another function of H2BK123ub1 is to promote histone H3 methylation at Lys4 (H3K4me) and Lys79 (H3K79me) in a mechanism of histone ''cross-talk'' referred to as trans-histone regulation (Briggs et al. 2002; Dover et al. 2002; Ng et al. 2002; Sun and Allis 2002). "
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    ABSTRACT: Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression.
    Genes & Development 08/2014; 28(15):1647-52. DOI:10.1101/gad.243121.114 · 10.80 Impact Factor
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    • "Histone H2B monoubiquitination (H2Bub) is part of a general mechanism that influences transcriptional activity positively (Weake and Workman, 2008). H2Bub was found to facilitate RNA Pol II processivity by favouring DNA accessibility, by helping to recruit the histone chaperone Facilitates Chromatin Transcription (FACT) and/or ensuring nucleosome reassembly upon RNA Pol II elongation (Belotserkovskaya et al., 2003; Pavri et al., 2006; Fleming et al., 2008; Xin et al., 2009; Fierz et al., 2011). In Saccharomyces cerevisiae a transcription-coupled cyclic process involves H2Bub by the Rad6-Bre1 ubiquitin ligase and subsequent deubiquitination by the SAGA complex. "
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    ABSTRACT: Research on the functional properties of nucleosome structure and composition dynamics has revealed that chromatin-level regulation is an essential component of light signalling and clock function in plants, two processes that rely extensively on transcriptional controls. In particular, several types of histone post-translational modifications and chromatin-bound factors act sequentially or in combination to establish transcriptional patterns and to fine-tune the transcript abundance of a large repertoire of light-responsive genes and clock components. Cytogenetic approaches have also identified light-induced higher-order chromatin changes that dynamically organize the condensation of chromosomal domains into sub-nuclear foci containing silenced repeat elements. In this review, we report recently identified molecular actors that establish chromatin state dynamics in response to light signals such as photoperiod, intensity, and spectral quality. We also highlight the chromatin-dependent mechanisms that contribute to the 24-h circadian gene expression and its impact on plant physiology and development. The commonalities and contrasts of light- and clock-associated chromatin-based mechanisms are discussed, with particular emphasis on their impact on the selective regulation and rapid modulation of responsive genes.
    Journal of Experimental Botany 02/2014; 65(11). DOI:10.1093/jxb/eru011 · 5.53 Impact Factor
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