A role of the CTCF binding site at enhancer E? in the dynamic chromatin organization of the Tcra-Tcrd locus.

ABSTRACT: The regulation of T cell receptor Tcra gene rearrangement has been extensively studied. The enhancer E? plays an essential role in Tcra rearrangement by establishing a recombination centre in the J? array and a chromatin hub for interactions between V? and J? genes. But the mechanism of the E? and its downstream CTCF binding site (here named EACBE) in dynamic chromatin regulation is unknown. The Hi-C data showed that the EACBE is located at the sub-TAD boundary which separates the Tcra-Tcrd locus and the downstream region including the Dad1 gene. The EACBE is required for long-distance regulation of the E? on the proximal V? genes, and its deletion impaired the Tcra rearrangement. We also noticed that the EACBE and E? regulate the genes in the downstream sub-TAD via asymmetric chromatin extrusion. This study provides a new insight into the role of CTCF binding sites at TAD boundaries in gene regulation.

SUBMITTER: Zhao H 

PROVIDER: S-EPMC7515734 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature