Promoter-proximal pausing of RNA polymerase II: an opportunity to regulate gene transcription.

Transcription of eukaryotic genes by RNA polymerase II (pol II) is a complex, highly regulated multiphasic process. Pol II pauses in the proximity of the promoter on a large fraction of transcribed genes. Transcription initiation and elongation of transcripts are under distinct control. Induced gene expression can thus be due to enhanced initiation and/or stimulated elongation. Pausing and resumption of the elongation of transcripts is under the control of transcription elongation factors. Three of them, P-TEFb, DSIF, and NELF have been well characterized as protein complexes with multiple general but also gene specific functions. Elongation factors execute checkpoint functions but serve also as targets for signaling processes which regulate gene expression. Due to the general importance of transcription elongation factors, it is difficult to delineate the mechanisms by which elongation of specific genes is regulated by specific intracellular signals. However, it is clear that the controlled pausing of pol II provides an opportunity to finely control timing and quantity of transcriptional output.