PLX219113

GSE62483: T-bet recruits P-TEFb to super-enhancers to regulate T helper cell differentiation (RNA-Seq)

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The transcription factor T-bet induces differentiation of CD4+ T cells into the Th1 lineage and also allows for a degree of functional plasticity. Here, we show that T-bet acts through super-enhancers to recruit the elongation factor P-TEFb. Th1-specific genes are poised for activation in Th2 cells and P-TEFb recruitment activates transcriptional elongation. T-bet also induces extensive P-TEFb binding at super-enhancers, where it acts to stimulate enhancer RNA transcription. P-TEFb inhibition selectively blocks activation of lineage-specific genes and reverses Th1-associated retinitis pathology. T-bet-mediated recruitment of P-TEFb to super-enhancers at otherwise poised genes provides a model for how lineage-specifying factors promote differentiation towards specific cell fates whilst maintaining a degree of functional plasticity. SOURCE: Richard Jenner (r.jenner@ucl.ac.uk) - Regulatory Genomics UCL Cancer Institute