TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4⁺CD8⁺ thymocytes.

ABSTRACT: Thymocyte development requires a complex orchestration of multiple transcription factors. Ablating either TCF-1 or HEB in CD4⁺CD8⁺ thymocytes elicits similar developmental outcomes including increased proliferation, decreased survival, and fewer late Tcra rearrangements. Here, we provide a mechanistic explanation for these similarities by showing that TCF-1 and HEB share ~7,000 DNA-binding sites genome wide and promote chromatin accessibility. The binding of both TCF-1 and HEB was required at these shared sites for epigenetic and transcriptional gene regulation. Binding of TCF-1 and HEB to their conserved motifs in the enhancer regions of genes associated with T cell differentiation promoted their expression. Binding to sites lacking conserved motifs in the promoter r

SUBMITTER: Emmanuel AO 

PROVIDER: S-EPMC6867931 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature