| First Author | Xing S | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 8 | Pages | 2211-2226 |
| PubMed ID | 30045946 | Mgi Jnum | J:266029 |
| Mgi Id | MGI:6201849 | Doi | 10.1084/jem.20171514 |
| Citation | Xing S, et al. (2018) Tle corepressors are differentially partitioned to instruct CD8(+) T cell lineage choice and identity. J Exp Med 215(8):2211-2226 |
| abstractText | Tle/Groucho proteins are transcriptional corepressors interacting with Tcf/Lef and Runx transcription factors, but their physiological roles in T cell development remain unknown. Conditional targeting of Tle1, Tle3 and Tle4 revealed gene dose-dependent requirements for Tle proteins in CD8(+) lineage cells. Upon ablating all three Tle proteins, generation of CD8(+) T cells was greatly diminished, largely owing to redirection of MHC-I-selected thymocytes to CD4(+) lineage; the remaining CD8-positive T cells showed aberrant up-regulation of CD4(+) lineage-associated genes including Cd4, Thpok, St8sia6, and Foxp3 Mechanistically, Tle3 bound to Runx-occupied Thpok silencer, in post-selection double-positive thymocytes to prevent excessive ThPOK induction and in mature CD8(+) T cells to silence Thpok expression. Tle3 also bound to Tcf1-occupied sites in a few CD4(+) lineage-associated genes, including Cd4 silencer and St8sia6 introns, to repress their expression in mature CD8(+) T cells. These findings indicate that Tle corepressors are differentially partitioned to Runx and Tcf/Lef complexes to instruct CD8(+) lineage choice and cooperatively establish CD8(+) T cell identity, respectively. |
