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Nat Commun. 2018 Apr 11;9(1):1394. doi: 10.1038/s41467-018-03895-5.

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

Author information

1
Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA.
2
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
3
Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA.
4
Departments of Biochemistry and Molecular Biophysics and Biological Sciences, Columbia University, New York, NY, 10032, USA.
5
Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, USA.
6
Department of Chemistry and Applied Biosciences, Laboratorium für Organische Chemie, ETH Zürich, 8093, Zürich, Switzerland.
7
Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA. muir@princeton.edu.

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.

PMID:
29643390
PMCID:
PMC5895630
DOI:
10.1038/s41467-018-03895-5
[Indexed for MEDLINE]
Free PMC Article

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