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

Marion Crespo (1, 2) , Annelaure Damont (3, 4, 5, 6, 7) , Melina Blanco (8) , Emmanuelle Lastrucci (1, 2) , Sara El Kennani (9, 1) , Côme Ialy-Radio (8) , Laila El Khattabi (8) , Samuel Terrier (3) , Mathilde Louwagie (1, 2) , Sylvie Kieffer-Jaquinod (1, 2) , Anne-Marie Hesse (1, 2) , Christophe Bruley (1, 2) , Sophie Chantalat (10, 6) , Jérôme Govin (1, 2) , François Fenaille (3, 11, 12, 4, 7) , Christophe Battail (1) , Julie Cocquet (8) , Delphine Pflieger (1, 2)

1 IRIG - Institut de Recherche Interdisciplinaire de Grenoble
2 UGA - Université Grenoble Alpes
3 LEMM - Laboratoire d'Etude du Métabolisme des Médicaments
4 MTS - Médicaments et Technologies pour la Santé
5 CEA - CEA- Saclay
6 Université Paris-Saclay
7 MetaboHUB-IDF
8 IC UM3 (UMR 8104 / U1016) - Institut Cochin
9 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
10 JACOB - Institut de Biologie François JACOB
11 LI-MS - Laboratoire Innovations en Spectrométrie de Masse pour la santé
12 SPI - Service de Pharmacologie et Immunoanalyse

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 acetyla-tion 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.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Biochimie [q-bio.BM]

Marion Crespo, Annelaure Damont, Melina Blanco, Emmanuelle Lastrucci, Sara El Kennani, et al.. Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes. Nucleic Acids Research, 2020, 48 (8), pp.4115-4138. ⟨10.1093/nar/gkaa163⟩. ⟨hal-02945580⟩