NFAT primes the human RORC locus for RORγt expression in CD4 + T cells - Institut Pasteur Access content directly
Journal Articles Nature Communications Year : 2019

NFAT primes the human RORC locus for RORγt expression in CD4 + T cells

Abstract

T helper 17 (Th17) cells have crucial functions in mucosal immunity and the pathogenesis of several chronic inflammatory diseases. The lineage-specific transcription factor, RORγt, encoded by the RORC gene modulates Th17 polarization and function, as well as thymocyte development. Here we define several regulatory elements at the human RORC locus in thy-mocytes and peripheral CD4 + T lymphocytes, with CRISPR/Cas9-guided deletion of these genomic segments supporting their role in RORγt expression. Mechanistically, T cell receptor stimulation induces cyclosporine A-sensitive histone modifications and P300/CBP acetylase recruitment at these elements in activated CD4 + T cells. Meanwhile, NFAT proteins bind to these regulatory elements and activate RORγt transcription in cooperation with NF-kB. Our data thus demonstrate that NFAT specifically regulate RORγt expression by binding to the RORC locus and promoting its permissive conformation.
Fichier principal
Vignette du fichier
Regulation of human RORgt gene expression Yahia-Cherbal NatComm2019[2].pdf (1.71 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

pasteur-02626213 , version 1 (26-05-2020)

Licence

Attribution

Identifiers

Cite

Hanane Yahia-Cherbal, Magda Rybczynska, Domenica Lovecchio, Tharshana Stephen, Chloé Lescale, et al.. NFAT primes the human RORC locus for RORγt expression in CD4 + T cells. Nature Communications, 2019, 10 (1), pp.4698. ⟨10.1038/s41467-019-12680-x⟩. ⟨pasteur-02626213⟩
52 View
66 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More