| First Author | Rodríguez-Caparrós A | Year | 2022 |
| Journal | J Immunol | Volume | 208 |
| Issue | 4 | Pages | 910-928 |
| PubMed ID | 35082160 | Mgi Jnum | J:322743 |
| Mgi Id | MGI:7257957 | Doi | 10.4049/jimmunol.2000864 |
| Citation | Rodriguez-Caparros A, et al. (2022) Differently Regulated Gene-Specific Activity of Enhancers Located at the Boundary of Subtopologically Associated Domains: TCRalpha Enhancer. J Immunol 208(4):910-928 |
| abstractText | Enhancers activate transcription through long-distance interactions with their cognate promoters within a particular subtopologically associated domain (sub-TAD). The TCRalpha enhancer (Ealpha) is located at the sub-TAD boundary between the TCRalpha and DAD1 genes and regulates transcription toward both sides in an approximately 1-Mb region. Analysis of Ealpha activity in transcribing the unrearranged TCRalpha gene at the 5'-sub-TAD has defined Ealpha as inactive in CD4(-)CD8(-) thymocytes, active in CD4(+)CD8(+) thymocytes, and strongly downregulated in CD4(+) and CD8(+) thymocytes and alphabeta T lymphocytes. Despite its strongly reduced activity, Ealpha is still required for high TCRalpha transcription and expression of TCRalphabeta in mouse and human T lymphocytes, requiring collaboration with distant sequences for such functions. Because ValphaJalpha rearrangements in T lymphocytes do not induce novel long-range interactions between Ealpha and other genomic regions that remain in cis after recombination, strong Ealpha connectivity with the 3'-sub-TAD might prevent reduced transcription of the rearranged TCRalpha gene. Our analyses of transcriptional enhancer dependence during T cell development and non-T lineage tissues at the 3'-sub-TAD revealed that Ealpha can activate the transcription of specific genes, even when it is inactive to transcribe the TCRalpha gene at the 5'-sub-TAD. Hence distinct requirements for Ealpha function are necessary at specific genes at both sub-TADs, implying that enhancers do not merely function as chromatin loop anchors that nucleate the formation of factor condensates to increase gene transcription initiated at their cognate promoters. The observed different regulated Ealpha activity for activating specific genes at its flanking sub-TADs may be a general feature for enhancers located at sub-TAD boundaries. |
