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Role of Transcription Factors in Pausing RNA Polymerase II in Drosophila
註釋Promoter proximal pausing of RNA Polymerase II (Pol II) occurs on thousands of genes in animal cells. This pausing often correlates with rapid induction of genes, but direct tests of the relationship between pausing and induction rates are lacking. Hsp70 and hsp26 in Drosophila are rapidly induced by heat shock. Contrary to current expectations, depletion of NELF, a key factor in setting up the paused Pol II, disrupted pausing but did not interfere with rapid induction. Instead, depletion of NELF delayed the time when these genes shut off during recovery from heat shock. Further analyses showed that NELF-depletion delayed the dissociation of HSF from hsp70 and hsp26, and a similar delay was observed when CBP was depleted from cells. CBP has been reported to associate with Pol II, and acetylation of HSF by CBP has been implicated in dissociating HSF from heat shock genes. I propose that NELF-mediated pausing allows Pol II to direct CBP-mediated acetylation of HSF, thus causing HSF to dissociate from the gene. Activators are typically viewed as controlling Pol II transcription. My results reveal a reciprocal relationship in which the pausing of Pol II by NELF influences the interaction of the activator.