| First Author | Dai R | Year | 2023 |
| Journal | Nucleic Acids Res | Volume | 51 |
| Issue | 17 | Pages | 8987-9000 |
| PubMed ID | 37534534 | Mgi Jnum | J:340808 |
| Mgi Id | MGI:7530341 | Doi | 10.1093/nar/gkad641 |
| Citation | Dai R, et al. (2023) Three-way contact analysis characterizes the higher order organization of the Tcra locus. Nucleic Acids Res 51(17):8987-9000 |
| abstractText | The generation of highly diverse antigen receptors in T and B lymphocytes relies on V(D)J recombination. The enhancer Ealpha has been implicated in regulating the accessibility of Valpha and Jalpha genes through long-range interactions during rearrangements of the T-cell antigen receptor gene Tcra. However, direct evidence for Ealpha physically mediating the interaction of Valpha and Jalpha genes is still lacking. In this study, we utilized the 3C-HTGTS assay, a chromatin interaction technique based on 3C, to analyze the higher order chromatin structure of the Tcra locus. Our analysis revealed the presence of sufficient information in the 3C-HTGTS data to detect multiway contacts. Three-way contact analysis of the Tcra locus demonstrated the co-occurrence of the proximal Jalpha genes, Valpha genes and Ealpha in CD4+CD8+ double-positive thymocytes. Notably, the INT2-TEAp loop emerged as a prominent structure likely to be responsible for bringing the proximal Jalpha genes and the Valpha genes into proximity. Moreover, the enhancer Ealpha utilizes this loop to establish physical proximity with the proximal Valpha gene region. This study provides insights into the higher order chromatin structure of the Tcra locus, shedding light on the spatial organization of chromatin and its impact on V(D)J recombination. |
