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An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability

Authors :
Kanishk Jain
Matthew R Marunde
Jonathan M Burg
Susan L Gloor
Faith M Joseph
Karl F Poncha
Zachary B Gillespie
Keli L Rodriguez
Irina K Popova
Nathan W Hall
Anup Vaidya
Sarah A Howard
Hailey F Taylor
Laylo Mukhsinova
Ugochi C Onuoha
Emily F Patteson
Spencer W Cooke
Bethany C Taylor
Ellen N Weinzapfel
Marcus A Cheek
Matthew J Meiners
Geoffrey C Fox
Kevin EW Namitz
Martis W Cowles
Krzysztof Krajewski
Zu-Wen Sun
Michael S Cosgrove
Nicolas L Young
Michael-Christopher Keogh
Brian D Strahl
Source :
eLife, Vol 12 (2023)
Publication Year :
2023
Publisher :
eLife Sciences Publications Ltd, 2023.

Abstract

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation.

Details

Language :
English
ISSN :
2050084X
Volume :
12
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.4578fc571e78426c9ad347f2e09aa9c9
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.82596