Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.

Abstract:

:Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Crespo M,Damont A,Blanco M,Lastrucci E,Kennani SE,Ialy-Radio C,Khattabi LE,Terrier S,Louwagie M,Kieffer-Jaquinod S,Hesse AM,Bruley C,Chantalat S,Govin J,Fenaille F,Battail C,Cocquet J,Pflieger D

doi

10.1093/nar/gkaa163

subject

Has Abstract

pub_date

2020-05-07 00:00:00

pages

4115-4138

issue

8

eissn

0305-1048

issn

1362-4962

pii

5809165

journal_volume

48

pub_type

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