Alternative Enhancer Usage and Targeted Polycomb Marking Hallmark Promoter Choice during T Cell Differentiation.
Fiche publication
Date publication
août 2020
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SEXTON Thomas
Tous les auteurs :
Maqbool MA, Pioger L, El Aabidine AZ, Karasu N, Molitor AM, Dao LTM, Charbonnier G, van Laethem F, Fenouil R, Koch F, Lacaud G, Gut I, Gut M, Amigorena S, Joffre O, Sexton T, Spicuglia S, Andrau JC
Lien Pubmed
Résumé
During thymic development and upon peripheral activation, T cells undergo extensive phenotypic and functional changes coordinated by lineage-specific developmental programs. To characterize the regulatory landscape controlling T cell identity, we perform a wide epigenomic and transcriptional analysis of mouse thymocytes and naive CD4 differentiated T helper cells. Our investigations reveal a dynamic putative enhancer landscape, and we could validate many of the enhancers using the high-throughput CapStarr sequencing (CapStarr-seq) approach. We find that genes using multiple promoters display increased enhancer usage, suggesting that apparent "enhancer redundancy" might relate to isoform selection. Furthermore, we can show that two Runx3 promoters display long-range interactions with specific enhancers. Finally, our analyses suggest a novel function for the PRC2 complex in the control of alternative promoter usage. Altogether, our study has allowed for the mapping of an exhaustive set of active enhancers and provides new insights into their function and that of PRC2 in controlling promoter choice during T cell differentiation.
Mots clés
CapSTARR-seq, T cell enhancerome, enhancer and promoter usage, enhancer redundancy, long-distance enhancer-promoter interactions
Référence
Cell Rep. 2020 Aug 18;32(7):108048