The role of chromatin organizer Satb1 in shaping TCR repertoire in adult thymus

Author:

Feng Delong1,Li Zhaoqiang1,Qin Litao23,Hao Bingtao123

Affiliation:

1. Guangdong Provincial Key Laboratory of Tumor Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

2. Medical Genetic Institute of Henan Province, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan 450003, P.R. China.

3. National Health Commission Key Laboratory of Birth Defects Prevention, Henan Key Laboratory of Population Defects Prevention, Zhengzhou, Henan 450003, P.R. China.

Abstract

T cells recognize the universe of foreign antigens with a diverse repertoire of T cell receptors generated by V(D)J recombination. Special AT-rich binding protein 1 (Satb1) is a chromatin organizer that plays an essential role in T cell development. Previous study has shown that Satb1 regulates the re-induction of recombinase Rag1 and Rag2 in CD4+CD8+ thymocytes, affecting the secondary rearrangement of the Tcra gene. Here, we detected the repertoires of four TCR genes, Tcrd, Tcrg, Tcrb, and Tcra, in the adult thymus, and explored the role of the Satb1 in shaping the TCR repertoires. We observed a strong bias in the V and J gene usages of the Tcrd and Tcrg repertoires in WT and Satb1-deleted thymocytes. Satb1 deletion had few effects on the V(D)J rearrangement and repertoire of the Tcrg, Tcrd, and Tcrb genes. The Tcra repertoire was severely impaired in Satb1-deleted thymocytes, while the primary rearrangement was relatively normal. We also found the CDR3 length of TCRα chain was significantly longer in Satb1-deleted thymocytes, which can be explained by the strong bias of the proximal Jα usage. Our results showed that Satb1 plays an essential role in shaping TCR repertoires in αβ T cells.

Publisher

Canadian Science Publishing

Subject

Genetics,Molecular Biology,General Medicine,Biotechnology

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