ORIGINAL RESEARCH article

Front. Immunol.

Sec. T Cell Biology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1613621

This article is part of the Research TopicThymus Research and Development: A New Look to the Past, Current Knowledge, and Future PerspectivesView all 11 articles

The insulator EACBE regulates V(D)J recombination of Tcrd gene by modulating chromatin organization

Provisionally accepted
Yongchang ZhuYongchang Zhu1,2Ranran DaiRanran Dai3,4Hao ZhaoHao Zhao5Junwei LuoJunwei Luo5Keyi LiKeyi Li5Wei XueWei Xue5Litao QinLitao Qin1Hongyuan PanHongyuan Pan5Shixiu LiaoShixiu Liao1*Bingtao HaoBingtao Hao2,6*
  • 1Henan Key Provincial Laboratory of Genetic Diseases and Functional Genomics, People's Hospital of Zhengzhou University, Zhengzhou university, zhengzhou, China
  • 2Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
  • 3RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
  • 4Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
  • 5Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangdong, China
  • 6Henan Eye Institute, Henan Academy of Innovations in Medical Science, zhengzhou, China

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T cell receptor (TCR) diversity, essential for the recognition of a wide array of antigens, is generated through V(D)J recombination. The Tcra and Tcrd genes reside within a shared genomic locus, with Tcrd rearrangement occurring first in the double-negative (DN) stage during thymocyte development. Elucidating the regulatory mechanisms governing Tcrd rearrangement is therefore crucial for understanding the developmental coordination of both Tcrd and Tcra rearrangements. Chromatin architecture, orchestrated by CTCF-cohesin complexes and their binding sites, plays a fundamental role in regulating V(D)J recombination of antigen receptor genes. In this study, we report that EACBE, a CTCF binding element (CBE) located downstream of the Tcra-Tcrd locus, regulates Tcrd rearrangement. EACBE promotes the usage of proximal Vδ gene segments by facilitating spatial proximity between the Tcrd recombination centre and these Vδ elements. Notably, EACBE counteracts the insulating effects of INTs, two CBEs that demarcate the proximal V region from the Dδ-Jδ-Cδ cluster, thereby enabling effective chromatin extrusion. Furthermore, EACBE indirectly shapes the Tcra repertoire through its influence on Tcrd rearrangement. These findings reveal a novel regulatory axis involving special chromatin configuration and highlight distinct roles for specific CTCF binding sites in modulating antigen receptor gene assembly.

Keywords: CTCF binding element, T cell receptor, V(D)J Recombination, Chromatin architecture, chromatin activity

Received: 17 Apr 2025; Accepted: 01 Jul 2025.

Copyright: © 2025 Zhu, Dai, Zhao, Luo, Li, Xue, Qin, Pan, Liao and Hao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Shixiu Liao, Henan Key Provincial Laboratory of Genetic Diseases and Functional Genomics, People's Hospital of Zhengzhou University, Zhengzhou university, zhengzhou, China
Bingtao Hao, Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China

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