Figure 2.

P-TEFb is released from the 7SK snRNP on chromatin. The 7SK snRNP complex (containing P-TEFb phosphorylated in the T-loop, (P)) occupies promoter-proximal regions of genes containing paused Pol II, DSIF and NELF. In response to stimulation, PPM1G is recruited by the canonical transcription factor (TF) to dephosphorylate the P-TEFb T-loop, disrupting its interaction with Hexim-7SK RNA and facilitating its release. Other P-TEFb releasing factors include DDX21 (which directly unwinds the 7SK RNA), and the splicing regulator SF2 (which liberates P-TEFb through interactions with exonic splicing sequences). Through T-loop re-phosphorylation, P-TEFb is re-activated to phosphorylate paused Pol II and the negative elongation factors to promote pause release. The arrow denotes the position of the TSS. TF, transcription factor.