Open AccessHistone H3.3 phosphorylation amplifies stimulation-induced transcription
Author(s) -
Anja Armache,
Shuang Yang,
Alexia Martínez de Paz,
Lexi Robbins,
Ceyda Durmaz,
Jin-Gyu Cheong,
Arjun Ravishankar,
Andrew W Daman,
Dughan J. Ahimovic,
Thaís Klevorn,
Yuan Yue,
Tanja Arslan,
Shu Lin,
Tanya Panchenko,
Joel Hrit,
Miao Wang,
Samuel Thudium,
Benjamin A. Garcia,
Erica Korb,
KarimJean Armache,
Scott B. Rothbart,
Sandra B. Hake,
C. David Allis,
Haitao Li,
Steven Z. Josefowicz
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2533-0
Subject(s) - histone h3 , histone methyltransferase , microbiology and biotechnology , chromatin , histone h2a , histone , histone code , chromatin remodeling , biology , corepressor , histone methylation , transcription (linguistics) , transcription coregulator , transcription factor , genetics , repressor , gene , gene expression , nucleosome , dna methylation , linguistics , philosophy
Complex organisms can rapidly induce select genes in response to diverse environmental cues. This regulation occurs in the context of large genomes condensed by histone proteins into chromatin. The sensing of pathogens by macrophages engages conserved signalling pathways and transcription factors to coordinate the induction of inflammatory genes 1-3 . Enriched integration of histone H3.3, the ancestral histone H3 variant, is a general feature of dynamically regulated chromatin and transcription 4-7 . However, how chromatin is regulated at induced genes, and what features of H3.3 might enable rapid and high-level transcription, are unknown. The amino terminus of H3.3 contains a unique serine residue (Ser31) that is absent in 'canonical' H3.1 and H3.2. Here we show that this residue, H3.3S31, is phosphorylated (H3.3S31ph) in a stimulation-dependent manner along rapidly induced genes in mouse macrophages. This selective mark of stimulation-responsive genes directly engages the histone methyltransferase SETD2, a component of the active transcription machinery, and 'ejects' the elongation corepressor ZMYND11 8,9 . We propose that features of H3.3 at stimulation-induced genes, including H3.3S31ph, provide preferential access to the transcription apparatus. Our results indicate dedicated mechanisms that enable rapid transcription involving the histone variant H3.3, its phosphorylation, and both the recruitment and the ejection of chromatin regulators.