Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation.

ABSTRACT: Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Among these, the TCRA gene enhancer (Eα) is in an open and unmethylated chromatin structure well before activation. Integrative analyses revealed that the HOXA5-9 transcription factors repress the Eα enhancer at early stages of T cell differentiation, while their decommission is re

SUBMITTER: Cieslak A 

PROVIDER: S-EPMC7478722 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature