Control of Foxp3 induction and maintenance by sequential histone acetylation and DNA demethylation.

ABSTRACT: Regulatory T (T_reg) cells play crucial roles in suppressing deleterious immune response. Here, we investigate how T_reg cells are mechanistically induced in vitro (iT_reg) and stabilized via transcriptional regulation of T_reg lineage-specifying factor Foxp3. We find that acetylation of histone tails at the Foxp3 promoter is required for inducing Foxp3 transcription. Upon induction, histone acetylation signals via bromodomain-containing proteins, particularly targets of inhibitor JQ1, and sustains Foxp3 transcription via a global or trans effect. Subsequently, Tet-mediated DNA demethylation of Foxp3 cis-regulatory elements, mainly enhancer CNS2, increases chromatin accessibility and protein binding, stabilizing Foxp3 transcription and obviating the

SUBMITTER: Li J 

PROVIDER: S-EPMC8711072 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature