Article

Histone H2B ubiquitination and beyond

Department of Biochemistry and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Epigenetics: official journal of the DNA Methylation Society (Impact Factor: 5.11). 08/2010; 5(6):460-8. DOI: 10.4161/epi.5.6.12314
Source: PubMed

ABSTRACT Regulation of Set1-COMPASS-mediated H3K4 methylation and Dot1-mediated H3K79 methylation by H2BK123 ubiquitination (H2Bub1) is an evolutionarily conserved trans-histone crosstalk mechanism. How H2Bub1 impacts chromatin structure and affects Set1-COMPASS/Dot1 functions has not been fully defined. Ubiquitin was proposed to bind proteins to physically bridge H2Bub1 with Set1-COMPASS/Dot1. Alternatively, the bulky ubiquitin was thought to be a "wedge" that loosens the nucleosome for factor access. Contrary to the latter possibility, recent discoveries provide evidence for nucleosome stabilization by H2Bub1 via preventing the constant H2A-H2B eviction. Recent data has also uncovered a "docking-site" on H2B for Set1-COMPASS. Collectively, these findings invoke a model, where ubiquitin acts as a "glue" to bind the nucleosome together for supporting Set1-COMPASS/Dot1 functions. This review provides an overview of these novel findings. Additionally, how H2Bub1 and its deubiquitination might alter the chromatin dynamics during transcription is discussed. Possible models for nucleosome stabilization by ubiquitin are also provided.

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Available from: Mahesh B Chandrasekharan, Aug 14, 2015
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    • "In particular, all the ESCRT-I subunits are involved in transcriptional regulation (Figs 1, 2, 4) and some of these components (Vps23 and Mvb12) contain the domain for binding to ubiquitylated proteins. Thus, we examined whether the ESCRT-I complex interacts with or modulates the ubiquitylation of histone H2B, a modification closely associated with the activation of transcription through the methylation of histone H3 at lysine residues 4 and 79 (Chandrasekharan et al. 2010; Song and Ahn 2010; Sun and Allis 2002). To examine histone ubiquitylation, we used a yeast strain containing the Flag-tagged HTB1 gene and the hemagglutinin (HA)-tagged UBI4 gene as WT. "
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    • "However, the precise functions of Lys 112 ubiquitination have yet to be fully defined. A previous report had shown ubiquitination of histone H2BK123 enhanced its binding activity and stabilized nucleosome (Chandrasekharan et al., 2010). It is implicated that methylation of HMGB1 at Lys112 reduces its DNA-binding ability through the substitution of Lys112 ubiquitination. "
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    • "These data are consistent with previous experiments showing that uH2B stabilizes nucleosomes in vivo (Chandrasekharan et al. 2009). These results suggest that USP49 bound at exons regulates local uH2B levels, thereby affecting nucleosome stability, a fundamental chromatin characteristic thought to play profound roles in transcription elongation and cotranscriptional splicing (Chandrasekharan et al. 2010; Dujardin et al. 2013). "
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