Figure 1

a | RNA polymerase II (Pol II) is associated with promoters at, and just downstream of, the transcription start site (TSS). The transcriptional state, position and composition of Pol II are variable and depend on factors that contribute to recruitment, initiation, pausing and release of Pol II. Recruitment of Pol II by general transcription factors (GTFs) results in the formation of a pre-initiation complex (PIC). After rapid Pol II initiation and entry into the pause site, Pol II pausing by negative elongation factor (NELF) and DRB-sensitivity-inducing factor (DSIF) occurs, facilitated by the core promoter elements and the +1 nucleosome. Positive transcription elongation factor-b (P-TEFb) mediates the release of paused Pol II by phosphorylating NELF, DSIF and the carboxy-terminal domain (CTD) of Pol II. DSIF becomes a positive elongation factor after phosphorylation. b | The transcription cycle is predominantly regulated near the TSS, at the steps of recruitment of Pol II to promoters, and release from the promoter-proximal pause site. These steps are most variable in terms of rate (as indicated by the dark blue shading of the boxes defining the steps). Other steps, such as transcription initiation and entry to the pause site, as well as transcription termination from the pause site, seem not to be as variable in rate and less subject to regulation (as indicated by the lighter blue shading of the boxes).