Dataset Information

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. Here, 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, 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast) Mus Musculus (mouse)

TISSUE(S): Testis, Cell Suspension Culture

SUBMITTER: Delphine PFLIEGER

LAB HEAD: Virginie Brun

PROVIDER: PXD015380 | Pride | 2020-03-26

REPOSITORIES: Pride

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Publications

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

Crespo Marion M Damont Annelaure A Blanco Melina M Lastrucci Emmanuelle E Kennani Sara El SE Ialy-Radio Côme C Khattabi Laila El LE Terrier Samuel S Louwagie Mathilde M Kieffer-Jaquinod Sylvie S Hesse Anne-Marie AM Bruley Christophe C Chantalat Sophie S Govin Jérôme J Fenaille François F Battail Christophe C Cocquet Julie J Pflieger Delphine D

Nucleic acids research 20200501 8

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 histon ...[more]

PMID: 32182340

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Project description:Chromatin structure and function is maintained by dynamic protein-protein and protein-nucleic acid interactions. Histones are a family of proteins that are abundant chromatin constituents and that carry numerous post-translational modifications (PTMs). Histone PTMs mediate a variety of biological activities, including recruitment of enzymatic readers, writers and erasers that modulate protein activities, DNA replication, transcription and repair. Individual histone molecules contain multiple co-existing PTMs some of which exhibit crosstalk, i.e. coordinated or mutually exclusive activities. We here present an integrated experimental and computational approach for systems level molecular characterization of PTMs and PTM crosstalk. Using wildtype and engineered mouse embryonic stem cells with perturbations in the Polycomb Repressive Complex 1 (PRC1, suz12-/-), PRC2 (Ring1A/b-/-) and DNA methyltransferases (Dnmt1/3a/3b-/-) we performed comprehensive PTM analysis of histone H3 tails. We identified unique histone H3 PTM features of each of the four cell lines and we detected common combinatorial PTM features across cell lines. Using quantitative middle-down proteomics combined with probabilistic and statistical data analysis we extracted histone H3 PTM profiles for all four mESC systems. PTM crosstalk emerged as mutually exclusive histone PTMs or coordinately regulated PTMs independent of histone peptide abundance in the four model systems. We detected positive crosstalk between adjacent mono-methylated marks but strong negative crosstalk among most of the seven characterized di- and tri-methylations on lysines. We report novel features of PTM interplay involving hitherto poorly characterized arginine methylation and lysine methylation sites in histone H3, including H3R2me, H3R8me and H3K37me, which exhibited specific PTM codes suggesting a particular role in chromatin. All histone H3 PTM data is available in our publicly available CrossTalkDB repository at http://crosstalkdb.bmb.sdu.dk

Dataset Information

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

Publications

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

Similar Datasets

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