Promoter-proximal regulation of gene transcription: Key factors involved and emerging role of general transcription factors in assisting productive elongation

Abstract

The pausing of RNA polymerase II (Pol II) at the promoter-proximal sites is a key rate-limiting step in gene expression. Cells have dedicated a specific set of proteins that sequentially establish pause and then release the Pol II from promoter-proximal sites. A well-controlled pausing and subsequent release of Pol II is crucial for the fine tuning of expression of genes including signal-responsive and developmentally-regulated ones. The release of paused Pol II broadly involves its transition from initiation to elongation. In this review article, we will discuss the phenomenon of Pol II pausing, the underlying mechanism, and also the role of different known factors, with an emphasis on general transcription factors, involved in this overall regulation. We will further discuss some recent findings suggesting a possible role (underexplored) of initiation factors in assisting the transition of transcriptionally-engaged paused Pol II into productive elongation.

Keywords: General transcription factor; P-TEFb; Pause-release; Promoter-proximal pausing; RNA Polymerase II; Super Elongation Complex; TFIID; Transcription.