| DRB-sensitivity inducing factor (DSIF), a heterodimer composed of SPT4 and SPT5, is capable of both facilitating and inhibiting RNA polymerase II (RNAPII) activity. DSIF, together with NELF (Negative Elongation Factor), inhibits RNAPII elongation, resulting in promoter proximal pausing of RNAPII as it awaits additional signaling to resume transcription. The release of promoter proximal pausing is signaled through phosphorylation of the RNAPII C-terminal domain (CTD) and NELF by positive transcription elongation factor (P-TEFb). P-TEFb also phosphorylates SPT5 at Thr4 within the evolutionarily conserved heptapeptide repeat motif. This phosphorylation event switches DSIF from a transcriptional repressor to an activator where it becomes a critical factor for transcriptional elongation. |
