We characterize the epigenetic mechanisms controlling T cell fate
Maintaining the integrity of the body depends on close and dynamic cooperation between conventional and regulatory T cells. The intracellular and environmental signals that regulate the programming and interactions of these two cellular populations, and the signalling pathways and transcription factor networks they mobilize, have been widely characterized over the past twenty years. The molecular mechanisms that integrate all these signals at the chromatin level, and that control de facto the development, differentiation and functions of T cells, remain unknown.
Through an integrative approach, from the animal to the cell nucleus, the group led by Dr. Olivier Joffre , associate Professor at the Toulouse University, characterises the epigenetic mechanisms that control the fate of T lymphocytes. In recent work, its members have shown in particular that lysine methyltransferase SETDB1 suppresses the genes associated with the Th1 lineage in Th2 lymphocytes undergoing differentiation, and that it thus controls the phenotypic and functional stability of these cells in vitro and in vivo. From a mechanistic point of view, they showed that SETDB1 acts by suppressing the activity of endogenous retroviruses that were co-opted during the evolution into cis-regulating modules of the Th1 genes (Immunity 2019: 629-644.e8). More generally, members of this group decipher the role of non-coding RNAs, transposable elements and several chromatin proteins in the response of conventional and regulatory T cells to environmental signals |
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