Transcription shapes genome-wide histone acetylation patterns

Abstract

Histone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. Using immunoblot and chromatin immunoprecipitation-sequencing in S. cerevisiae, here we show that the majority of histone acetylation is dependent on transcription. This dependency is partially explained by the requirement of RNA polymerase II (RNAPII) for the interaction of H4 histone acetyltransferases (HATs) with gene bodies. Our data also confirms the targeting of HATs by transcription activators, but interestingly, promoter-bound HATs are unable to acetylate histones in the absence of transcription. Indeed, HAT occupancy alone poorly predicts histone acetylation genome-wide, suggesting that HAT activity is regulated post-recruitment. Consistent with this, we show that histone acetylation increases at nucleosomes predicted to stall RNAPII, supporting the hypothesis that this modification is dependent on nucleosome disruption during transcription. Collectively, these data show that histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.

RSC primes the quiescent genome for hypertranscription upon cell-cycle re-entry

“…This is consistent with a previous study of a mixed population of saturated cultures where histone acetylation was found to occur later in exit [44]. Together, our results are in agreement with a recent study demonstrating that histone acetylation takes place mostly as a consequence of transcription [45].…”

RSC primes the quiescent genome for hypertranscription upon cell cycle re-entry

“…This is consistent with a previous study of a mixed population of saturated cultures where histone acetylation was found to occur later in exit[44]. Together, our results are in agreement with a recent study demonstrating that histone acetylation takes place mostly as a consequence of transcription [45].…”

“…This suggests that, while there was a strong transcriptional response during refeeding, histone acetylation was delayed. This result is in agreement with a recent study demonstrating that histone acetylation takes place mostly as a consequence of transcription [44].…”

“…2) Recent structural studies have shown that the nucleosome acidic patch is in direct contact with subunits of the RSC complex [62][63][64][65]. If the acidic patch is occluded by hypoacetylated H4 tails in quiescence for example [11,[66][67][68][69] is a consequence of transcription [44]. In a separate study, we recently found that the SWI/SNF remodeling enzyme promotes transcription of a subset of hypoacetylated genes during quiescence entry, implying a specialized transcription regulation program for essential genes in the wake of widespread transcriptional shutdown [57].…”

“…Indeed, transcription appears to play a prominent role in RSC localization: RSC moves into gene bodies during transcription activation and this movement is blocked when transcription is inhibited, as we have reported above. It is likely that a combination of transcription and histone acetylation helps pull RSC into gene bodies, given recent work showing that acetylation is a consequence of transcription [44]. In a separate study, we recently found that the SWI/SNF remodeling enzyme promotes transcription of a subset of hypoacetylated genes during quiescence entry, implying a specialized transcription regulation program for essential genes in the wake of widespread transcriptional shutdown [57].…”