Article

Histone H2B C-terminal helix mediates trans-histone H3K4 methylation independent of H2B ubiquitination.

Department of Biochemistry, Vanderbilt University School of Medicine, 613C Light Hall, Nashville, TN 37232, USA.
Molecular and Cellular Biology (Impact Factor: 5.04). 07/2010; 30(13):3216-32. DOI: 10.1128/MCB.01008-09
Source: PubMed

ABSTRACT The trans-histone regulatory cross talk between H2BK123 ubiquitination (H2Bub1) and H3K4 and H3K79 methylation is not fully understood. In this study, we report that the residues arginine 119 and threonine 122 in the H2B C-terminal helix are important for transcription and cell growth and play a direct role in controlling H2Bub1 and H3K4 methylation. These residues modulate H2Bub1 levels by controlling the chromatin binding and activities of the deubiquitinases. Furthermore, we find an uncoupling of the H2Bub1-mediated coregulation of both H3K4 and -K79 methylation, as these H2B C-terminal helix residues are part of a distinct surface that affects only Set1-COMPASS (complex proteins associated with Set1)-mediated H3K4 methylation without affecting the functions of Dot1. Importantly, we also find that these residues interact with Spp1 and control the chromatin association, integrity, and overall stability of Set1-COMPASS independent of H2Bub1. Therefore, we have uncovered a novel role for the H2B C-terminal helix in the trans-histone cross talk as a binding surface for Set1-COMPASS. We provide further insight into the trans-histone cross talk and propose that H2Bub1 stabilizes the nucleosome by preventing H2A-H2B eviction and, thereby, retains the "docking site" for Set1-COMPASS on chromatin to maintain its stable chromatin association, complex stability, and processive methylation.

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    • "A previous study reported that mutational alteration of H2B arginine 119 to alanine does not prevent H2BK123 mono-ubiquitination, but does affect the degree of H3K4 methylation (Chandrasekharan et al. 2010). As previously reported, changing H2BR119 to alanine (H2BR119A) reduces the chromatin association of Spp1 and therefore H3K4 tri-methylation, whereas changing H2B119 to aspartic acid (H2BR119D) results in loss of H3K4 di-and trimethylation to the same extent as eliminating H2BK123 mono-ubiquitination (Chandrasekharan et al. 2010). Our analysis of these histone H2B mutants revealed that strains expressing htb1-R119D displayed elevated plasmid loss rates similar to those of the htb1-K123R strain (Figure 6C). "
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