Stepwise activities of mSWI/SNF family chromatin remodeling complexes direct T cell activation and exhaustion.

ABSTRACT: Highly coordinated changes in gene expression underlie T cell activation and exhaustion. However, the mechanisms by which such programs are regulated and how these may be targeted for therapeutic benefit remain poorly understood. Here, we comprehensively profile the genomic occupancy of mSWI/SNF chromatin remodeling complexes throughout acute and chronic T cell stimulation, finding that stepwise changes in localization over transcription factor binding sites direct site-specific chromatin accessibility and gene activation leading to distinct phenotypes. Notably, perturbation of mSWI/SNF complexes using genetic and clinically relevant chemical strategies enhances the persistence of T cells with attenuated exhaustion hallmarks and increased memory features in vitro and in vivo. Finally, phar

SUBMITTER: Battistello E 

PROVIDER: S-EPMC10121856 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature