Transcription regulation through promoter-proximal pausing of RNA polymerase II

Abstract

Recent work has shown that the RNA polymerase II enzyme pauses at a promoter-proximal site of many genes in Drosophila and mammals. This rate-limiting step occurs after recruitment and initiation of RNA polymerase II at a gene promoter. This stage in early elongation appears to be an important and broadly used target of gene regulation.

Fig. 1

Regulation of entry and escape of Pol II at pause sites. The rate of pause site entry (yellow arrows—wide arrow, fast entry; narrow arrow, slow entry) is defined as the rate at which Pol II (red) enters a pause site when it is freely accessible. The relative rates of entry and escape (green arrow) produce the observed patterns of Pol II density (blue line). (A) Pol II cannot access the promoter and transcription is “off.” (B) A potentiated state through the setup of a promoter-proximal paused Pol II by factors that promote entry (yellow oval). NELF (pentagon) and DSIF (blue oval) stabilize the paused Pol II. (C) Fully activated transcription requires factors that promote escape (green rectangle). Also, single factors can have one or both types of activation domains that in turn can be regulated by reversible modifications and associations.