Mots-Clés
transcriptomic
epigenomic
promoter-capture
germ cells
Description
Summary of the host research topics:
The present master project will be co-supervised by the teams of Dr Christophe Battail (CEA Grenoble, host team) and Dr Julie Cocquet (Institut Cochin, Paris). Our groups have established a years-long collaboration to investigate gene and chromatin regulation during spermatogenesis at the molecular level, with particular interest in histone marks dynamics across male germ cell differentiation (Crespo et al. 2020; Blanco et al., 2023; Coulée et al., 2025). Our current work focuses on the characterization by high-throughput technologies of novel histone marks (i.e. lactylation) whose levels depend upon the cell’s metabolic activity. Thus, by applying integrative multi-omic data analyses (transcriptomic, ChIPseq/CUT&Tag, promoter capture Hi-C), we study how histone marks interplay with the 3D genome to regulate gene expression, and their sensitivity to external factors (metabolic stress).
Title of the internship:
Integration of transcriptomic, epigenomic and 3D genome data to better understand the chromatin code during male germ cell differentiation
Project:
Spermatogenesis is a complex process of cell differentiation that requires an extremely tight regulation at different levels, during which the chromatin is extensively remodeled. It consists in three phases that present very different gene expression programs, correlating with dynamic chromatin environments in terms of histone post-translational modifications (PTMs). While the fast recent advances in the latest years have allowed the characterization of the three-dimensional (3D) genome structure as an additional layer of regulation during spermatogenesis, the resolution achieved by conventional Hi-C (50Kbp) is not enough to resolve promoter interactions with other distal regulatory regions, thus limiting our understanding about the chromatin dynamics during this process.
To overcome this challenge, we have recently generated promoter capture Hi-C (PCHi-C) data in 3 male germ cell types, each representing a spermatogenic phase, which have allowed us to assign genomic contacts between promoters and distal regulatory regions at an unprecedented level of resolution of 3Kbp. Thus, the proposed master project aims at performing integrative multi-omic downstream analyses of this complex map of promoter interactions with RNA-seq and ChIP-seq/CUT&Tag datasets to generate a comprehensive understanding of chromatin dynamics during male germ cell development.
We are searching for a highly motivated candidate with hands-on experience in omics data analysis and/or integration, strong skills in Python, R and Bash, experience working in Linux and cluster computing environments, with applied critical thinking and eagerness to further develop their bioinformatics skills.
The candidate will be involved in the integration of PCHi-C data with our model of chromatin environment based on ChromHMM (Ernst et al., 2017; Coulée et al., 2025), to identify which histone marks are associated with the identified interactions and annotate distal regulatory regions. Then, the map of promoter interactions will be correlated with transcriptomic datasets, to identify the dynamics of the genomic interactions during male germ cell development in association with gene expression. And, finally, to integrate PCHi-C data with recently produced CUT&Tag datasets against different histone lactylation marks, to better understand the role of these uncharacterized histone marks during male germ cell development.
References:
Blanco M, El Khattabi L, Gobé C, Crespo M, Coulée M, de la Iglesia A, Ialy-Radio C, Lapoujade C, Givelet M, Delessard M, Seller-Corona I, Yamaguchi K, Vernet N, Van Leeuwen F, Lermine A, Okada Y, Daveau R, Oliva R, Fouchet P, Ziyyat A, Pflieger D, Cocquet J. DOT1L regulates chromatin reorganization and gene expression during sperm differentiation. EMBO Rep. 2023 Jun 5;24(6):e56316
Coulée M, de la Iglesia A, Blanco M, Gobé C, Lapoujade C, Ialy-Radio C, Alvarez-Gonzalez L, Meurice G, Ruiz-Herrera A, Fouchet P, Cocquet J, El Khattabi L. Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells. Commun Biol. 2025 Jan 28;8(1):138
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. Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes. Nucleic Acids Res. 2020 May 7;48(8):4115-4138
Ernst J, Kellis M. Chromatin-state discovery and genome annotation with ChromHMM. Nat Protoc. 2017 Dec;12(12):2478-2492. doi: 10.1038/nprot.2017.124.