Alternative enhancer usage and targeted polycomb marking hallmark promoter choice during T cell differentiation

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  • dc.contributor.author Maqbool, Muhammad Ahmad
  • dc.contributor.author Pioger, Léo
  • dc.contributor.author El Aabidine, Amal Zine
  • dc.contributor.author Karasu, Nezih
  • dc.contributor.author Molitor, Anne Marie
  • dc.contributor.author Dao, Lan T.M.
  • dc.contributor.author Charbonnier, Guillaume
  • dc.contributor.author van Laethem, François
  • dc.contributor.author Fenouil, Romain
  • dc.contributor.author Koch, Frederic
  • dc.contributor.author Lacaud, Georges
  • dc.contributor.author Gut, Ivo Glynne
  • dc.contributor.author Gut, Marta
  • dc.contributor.author Amigorena, Sebastian
  • dc.contributor.author Joffre, Olivier
  • dc.contributor.author Sexton, Thomas
  • dc.contributor.author Spicuglia, Salvatore
  • dc.contributor.author Andrau, Jean-Christophe
  • dc.date.accessioned 2020-10-27T06:49:40Z
  • dc.date.available 2020-10-27T06:49:40Z
  • dc.date.issued 2020
  • dc.description.abstract 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.
  • dc.description.sponsorship 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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. Alternative enhancer usage and targeted polycomb marking hallmark promoter choice during T cell differentiation. Cell Rep. 2020; 32(7):108048. DOI: 10.1016/j.celrep.2020.108048
  • dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2020.108048
  • dc.identifier.issn 2211-1247
  • dc.identifier.uri http://hdl.handle.net/10230/45580
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Cell Rep. 2020; 32(7):108048
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/678624
  • dc.rights © 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/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword CapSTARR-seq
  • dc.subject.keyword T cell enhancerome
  • dc.subject.keyword Enhancer and promoter usage
  • dc.subject.keyword Enhancer redundancy
  • dc.subject.keyword Long-distance enhancer-promoter interactions
  • dc.title Alternative enhancer usage and targeted polycomb marking hallmark promoter choice during T cell differentiation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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