Question

During embryonic development, there are many promoters where RNA Polymerase II is bound, but not allowed to initiate transcription. These are called poised promoters. Are the transcription factors that initiate expression of poised promoters more likely to modify chromatin or interact directly with the polymerase? Justify your answer

Answer 1

During embryonic development , the phenomenon of pause in transcription elongation is a widely accepted method of temporal gene regulation. In this mechanism, RNA Pol II binds the promoter along with the basal transcription factors and form the pre-initiation complex. But after 9-10 nucleotide long nascent RNA emergence, the RNA Pol II escapes the promoter and a Serine phosphorylation at the C terminal domain occur. After elongation giving rise to 25-40 nt, the RNA Pol II stalls and only enter into productive elongation after the pause release. This pause is brought about by several factors like DRB sensitivity inducing factor (DSIF) and Negative elongation factor (NELF) and Gdown1. While the first two possibly interact with the nascent RNA molecule, the 3rd is known to interact with RNA Pol II directly to stabilize the poised state.

Since the whole pausing phenomenon occurs due to the involvement of factors that bind RNA Pol II or nascent RNA and does not involve chromatin condensation to abort transcription transiently, it is more likely that the transcription factors that initiate expression of poised promoter, interact directly with RNA Pol II ,rather than with histone proteins.

Indeed research confirmed that pausing is overcome by the action of Positive transcription elongation factor b (P-TEFb) which interact with DSIF, NELF and RNA Pol II CTD and phosphorylate them to re-initiate transcription.

In few cases these poised promoters ,rich in special promoter elements like Motif Ten Element (MTE) , Pause Button (PB) also have intrinsic properties leading them to associate with nucleosome instead of RNA Pol II. This nucleosome association is antagonized by the binding of GAGA factor to the promoter and GAGA factor help recruit poised Pol II along with NELF. The transcription factors that ultimately initiate transcription at these sites, such as P-TEFb, interact directly with the Pol II-NELF complex and lifts the pause.