H3K9 post-translational modifications regulate epiblast/primitive endoderm specification in rabbit blastocysts

Archive ouverte

Bouchereau, Wilhelm | Samruan, Worawalan | Pham, Hong, Thu | Afanassieff, Marielle | Savatier, Pierre | Parnpai, Rangsun | Beaujean, Nathalie

Edité par CCSD -

International audience. Post-translational modifications of histone H3 on lysine 9, specifically acetylation (H3K9ac) and tri-methylation (H3K9me3), play a critical role in regulating chromatin accessibility. However, the role of these modifications in lineage segregation in the mammalian blastocyst is poorly understood. We demonstrate that the tri-methylation mark, H3K9me3, is more abundant in the parietal endoderm and trophectoderm compared to the inner cell mass and epiblast of rabbit blastocysts. Conversely, H3K9ac is more evenly distributed among all lineages, with a noticeable decrease during the transition from inner cell mass to epiblast. These distinct distributions correlate with specific patterns of gene expression in histone-modifying enzymes, including methyltransferases (EHMT1, EHMT2, SETDB1), acetyltransferases (KAT6B, EP300, CREBBP), and deacetylases (HDAC1, HDAC5, HDAC8). Disrupting H3K9me3 using an EHMT1/2 inhibitor impairs primitive endoderm segregation, while inhibiting H3K9ac through a class I HDAC inhibitor favors epiblast expansion over primitive endoderm. These changes influence genes associated with pluripotency and lineage determination, underscoring the significance of H3K9 modifications in embryonic cell fate decisions. Moreover, this approach was used to facilitate the propagation of naive rabbit embryonic stem cells (ESCs). Treatment with a class I HDAC inhibitor notably increases the derivation efficiency and pluripotent properties of rabbit ESCs, enhancing their ability to colonize embryos when reintroduced into early-stage embryos.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion