| First Author | Hertweck A | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 12 | Pages | 2756-70 |
| PubMed ID | 27292648 | Mgi Jnum | J:238297 |
| Mgi Id | MGI:5819009 | Doi | 10.1016/j.celrep.2016.05.054 |
| Citation | Hertweck A, et al. (2016) T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex. Cell Rep 15(12):2756-70 |
| abstractText | The transcription factor T-bet directs Th1 cell differentiation, but the molecular mechanisms that underlie this lineage-specific gene regulation are not completely understood. Here, we show that T-bet acts through enhancers to allow the recruitment of Mediator and P-TEFb in the form of the super elongation complex (SEC). Th1 genes are occupied by H3K4me3 and RNA polymerase II in Th2 cells, while T-bet-mediated recruitment of P-TEFb in Th1 cells activates transcriptional elongation. P-TEFb is recruited to both genes and enhancers, where it activates enhancer RNA transcription. P-TEFb inhibition and Mediator and SEC knockdown selectively block activation of T-bet target genes, and P-TEFb inhibition abrogates Th1-associated experimental autoimmune uveitis. T-bet activity is independent of changes in NF-kappaB RelA and Brd4 binding, with T-bet- and NF-kappaB-mediated pathways instead converging to allow P-TEFb recruitment. These data provide insight into the mechanism through which lineage-specifying factors promote differentiation of alternative T cell fates. |
