RT Journal Article
SR Electronic
T1 An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.28.482307
DO 10.1101/2022.02.28.482307
A1 Kanishk Jain
A1 Matthew R. Marunde
A1 Jonathan M. Burg
A1 Susan L. Gloor
A1 Faith M. Joseph
A1 Zachary B. Gillespie
A1 Keli L. Rodriguez
A1 Sarah A. Howard
A1 Irina K. Popova
A1 Nathan W. Hall
A1 Anup Vaidya
A1 Spencer W. Cooke
A1 Kevin E. W. Namitz
A1 Bethany C. Taylor
A1 Ellen N. Weinzapfel
A1 Marcus A. Cheek
A1 Matthew J. Meiners
A1 Krzysztof Krajewski
A1 Michael S. Cosgrove
A1 Nicolas L. Young
A1 Michael-Christopher Keogh
A1 Brian D. Strahl
YR 2022
UL http://biorxiv.org/content/early/2022/02/28/2022.02.28.482307.abstract
AB In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The DNA-bound state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (K9ac, K14ac, K18ac) is linked to increased engagement of H3K4me3 by the BPTF PHD finger, but it is unknown if this mechanism has broader extension. Here we show that cis H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and further extends to H3K4 writers, notably methyltransferase MLL1. This regulation is nucleosome-dependent and also observed in vivo, where H3 acetylation correlates with increased levels of cis H3K4me. These observations reveal an acetylation ‘chromatin switch’ on the H3 N-terminal tail that modulates the accessibility and function of H3K4 methylation in chromatin. Our findings also resolve the long-standing question of why H3K4me3 levels are linked with H3 acetylation.Competing Interest StatementEpiCypher is a commercial developer and supplier of reagents (e.g. PTM-defined semi-synthetic nucleosomes; dNucs and versaNucs) and platforms (dCypher) used in this study.