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

A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra-Tcrd locus.
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增强子 E α 处 CTCF 结合位点在 Tcra-Tcrd 基因座动态染色质组织中的作用

DOI:
10.1093/nar/gkaa711
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发表时间:
2020-09-25
影响因子:
14.9
通讯作者:
Hao B
Hao B
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao H;Li Z;Zhu Y;Bian S;Zhang Y;Qin L;Naik AK;He J;Zhang Z;Krangel MS;Hao B

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T细胞受体Tcra基因重排的调控已被广泛研究。增强子Eα通过在Jα阵列中建立重组中心以及Vα和Jα基因之间相互作用的染色质枢纽,在Tcra重排中起重要作用。但Eα及其下游CTCF结合位点(EACBE)在染色质动态调控中的作用机制尚不清楚。Hi-C数据显示EACBE位于Tcra-Tcrd位点和下游区域(包括Dad 1基因)之间的亚细胞边界。EACBE是近端Vα基因上的Eα长距离调控所必需的,其缺失损害了Tcra重排。我们还注意到EACBE和Eα通过不对称染色质挤出调控下游亚细胞的基因。这项研究提供了一个新的见解CTCF结合位点的作用,在基因调控的边界。
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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