Guangdong Provincial Key Laboratory of Tumor Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Henan Medical Genetics Institute, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan Province, China.
Nucleic Acids Res. 2020 Sep 25;48(17):9621-9636. doi: 10.1093/nar/gkaa711.
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.
T 细胞受体 Tcra 基因重排的调控已得到广泛研究。增强子 Eα 通过在 Jα 簇中建立一个重组中心以及一个 Vα 和 Jα 基因相互作用的染色质中心，在 Tcra 重排中发挥着重要作用。但是，Eα 及其下游 CTCF 结合位点（此处命名为 EACBE）在动态染色质调控中的机制尚不清楚。Hi-C 数据显示，EACBE 位于亚 TAD 边界处，该边界分隔了 Tcra-Tcrd 基因座和包括 Dad1 基因在内的下游区域。EACBE 是 Eα 对近端 Vα 基因进行长距离调控所必需的，其缺失会损害 Tcra 重排。我们还注意到，EACBE 和 Eα 通过不对称染色质外推来调节下游亚 TAD 中的基因。本研究为 TAD 边界处 CTCF 结合位点在基因调控中的作用提供了新的见解。
