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

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. Overall design: Strand-specific total and poly-A+ RNA-Seq in Th1 and Th2 cells from two independent donors

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Hertweck A, Evans CM, Eskandarpour M, Lau JC, Oleinika K, Jackson I, Kelly A, Ambrose J, Adamson P, Cousins DJ, Lavender P, Calder VL, Lord GM, Jenner RG