2026-04-05T10:44:12Zhttps://recercat.cat/oai/requestoai:recercat.cat:10230/455802025-12-12T03:31:28Zcom_2072_6col_2072_452952
Alternative enhancer usage and targeted polycomb marking hallmark promoter choice during T cell differentiation
Maqbool, Muhammad Ahmad
Pioger, Léo
El Aabidine, Amal Zine
Karasu, Nezih
Molitor, Anne Marie
Dao, Lan T.M.
Charbonnier, Guillaume
van Laethem, François
Fenouil, Romain
Koch, Frederic
Lacaud, Georges
Gut, Ivo Glynne
Gut, Marta
Amigorena, Sebastian
Joffre, Olivier
Sexton, Thomas
Spicuglia, Salvatore
Andrau, Jean-Christophe
CapSTARR-seq
T cell enhancerome
Enhancer and promoter usage
Enhancer redundancy
Long-distance enhancer-promoter interactions
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.
This work was supported in J.-C.A.’s lab by grants from Fondation pour la Recherche Médicale (FRM) “Amorçage Jeunes Equipes” AJE20130728183, Agence Nationale de la Recherche (ANR) isplice (ANR-11-BSV8-0013), ANR ChromaTin (ANR-10-BLAN-1326), ITMO INCA “Dys3Dpoly,” ESGI 2011 (FP7 funding for high-throughput sequencing), and Ligue Régionale contre le Cancer (Hérault). L.P. was supported by a grant from FRM (4eme année thèse FDT201904007910). The T.S. lab was supported by funds from the European Research Council (ERC) (H2020, Starting Grant 678624 - CHROMTOPOLOGY), the ATIP-Avenir program, and the grant ANR-10-LABX-0030-INRT, under program ANR-10-IDEX-0002-02. A.M.M. is supported by funds from IDEX (University of Strasbourg) and the Institut National Du Cancer.
2020-10-27T06:49:40Z
2020-10-27T06:49:40Z
2020
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Cell Rep. 2020; 32(7):108048
info:eu-repo/grantAgreement/EC/H2020/678624
© 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Elsevier