Functional crosstalk between histone H2B ubiquitylation and H2A modifications and variants.

TitleFunctional crosstalk between histone H2B ubiquitylation and H2A modifications and variants.
Publication TypeJournal Article
Year of Publication2018
AuthorsWojcik, F, Dann, GP, Beh, LY, Debelouchina, GT, Hofmann, R, Muir, TW
JournalNat Commun
Volume9
Issue1
Pagination1394
Date Published2018 Apr 11
ISSN2041-1723
Abstract

Ubiquitylation of histone H2B at lysine residue 120 (H2BK120ub) is a prominent histone posttranslational modification (PTM) associated with the actively transcribed genome. Although H2BK120ub triggers several critical downstream histone modification pathways and changes in chromatin structure, less is known about the regulation of the ubiquitylation reaction itself, in particular with respect to the modification status of the chromatin substrate. Here we employ an unbiased library screening approach to profile the impact of pre-existing chromatin modifications on de novo ubiquitylation of H2BK120 by the cognate human E2:E3 ligase pair, UBE2A:RNF20/40. Deposition of H2BK120ub is found to be highly sensitive to PTMs on the N-terminal tail of histone H2A, a crosstalk that extends to the common histone variant H2A.Z. Based on a series of biochemical and cell-based studies, we propose that this crosstalk contributes to the spatial organization of H2BK120ub on gene bodies, and is thus important for transcriptional regulation.

DOI10.1038/s41467-018-03895-5
Alternate JournalNat Commun
PubMed ID29643390
PubMed Central IDPMC5895630
Grant ListP01 CA196539 / CA / NCI NIH HHS / United States
R01 GM107047 / GM / NIGMS NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States