A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra–Tcrd locus
Zhao Hao, Li Zhaoqiang, Zhu Yongchang, Bian Shasha, Zhang Yan, Qin Litao, Naik Abani Kanta, He Jiangtu, Zhang Zhenhai, Krangel Michael S, Hao Bingtao
Journal:NUCLEIC ACIDS RESEARCH
IF:11.5
DOI:10.1093/nar/gkaa711
PMID:
Published:2020-08-27
research field:神经科学分子生物学细胞生物学免疫学心血管生物学基因组学
Abstract
Abstract The regulation of T cell receptor Tcra gene rearrangement has been extensively studied. The enhancer Eα plays an essential role in Tcra rearrangement by establishing a recombination centre in the Jα array and a chromatin hub for interactions between Vα and Jα genes. But the mechanism of the Eα 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 Eα on the proximal Vα genes, and its deletion impaired the Tcra rearrangement. We also noticed that the EACBE and Eα 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.
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