A unique histone 3 lysine 14 chromatin signature underlies tissue-specific gene regulation.

Autor: Regadas I; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden., Dahlberg O; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden., Vaid R; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden., Ho O; Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75237, Uppsala, Sweden., Belikov S; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden., Dixit G; Department of Genome Sciences, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia., Deindl S; Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, 75237, Uppsala, Sweden., Wen J; Department of Genome Sciences, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2600, Australia. Electronic address: jiayu.wen@anu.edu.au., Mannervik M; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden. Electronic address: mattias.mannervik@su.se.
Jazyk: angličtina
Zdroj: Molecular cell [Mol Cell] 2021 Apr 15; Vol. 81 (8), pp. 1766-1780.e10. Date of Electronic Publication: 2021 Feb 24.
DOI: 10.1016/j.molcel.2021.01.041
Abstrakt: Organismal development and cell differentiation critically depend on chromatin state transitions. However, certain developmentally regulated genes lack histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac, respectively) and histone 3 lysine 4 (H3K4) methylation, histone modifications common to most active genes. Here we describe a chromatin state featuring unique histone 3 lysine 14 acetylation (H3K14ac) peaks in key tissue-specific genes in Drosophila and human cells. Replacing H3K14 in Drosophila demonstrates that H3K14 is essential for expression of genes devoid of canonical histone modifications in the embryonic gut and larval wing imaginal disc, causing lethality and defective wing patterning. We find that the SWI/SNF protein Brahma (Brm) recognizes H3K14ac, that brm acts in the same genetic pathway as H3K14R, and that chromatin accessibility at H3K14ac-unique genes is decreased in H3K14R mutants. Our results show that acetylation of a single lysine is essential at genes devoid of canonical histone marks and uncover an important requirement for H3K14 in tissue-specific gene regulation.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE