Promoter proximal pausing on genes in metazoans

The past two decades of research into transcriptional control of protein-encoding genes in eukaryotes have focused on regulatory mechanisms that act by controlling the recruitment of Pol II to a gene's promoter. Recent genome-wide analyses of the distribution of Pol II indicates that Pol II is concentrated in the promoter regions of thousands of genes in human and Drosophila cells. In many cases, Pol II may have initiated transcription but paused in the promoter proximal region. Hence, release of Pol II from the promoter region into the body of a gene is now recognized as a common rate-limiting step in the control of gene expression. Notably, most genes with paused Pol II are expressed indicating that the pause can be transient. What causes Pol II to concentrate in the promoter region and how it is released to transcribe a gene are the focus of this review.