Alternative Enhancer Usage and Targeted Polycomb Marking Hallmark Promoter Choice during T Cell Differentiation

Muhammad Ahmad Maqbool, Léo Pioger, Amal Zine El Aabidine, Nezih Karasu, Anne Marie Molitor, Lan T M Dao, Guillaume Charbonnier, Francois van Laethem, Romain Fenouil, Frederic Koch, Georges Lacaud, Ivo Gut, Marta Gut, Sebastian Amigorena, Olivier Joffre, Thomas Sexton, Salvatore Spicuglia, Jean-Christophe Andrau

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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.

Original languageEnglish
Pages (from-to)108048
JournalCell Reports
Issue number7
Publication statusPublished - 18 Aug 2020

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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