Distinct transcriptional roles for Histone H3-K56 acetylation during the cell cycle in Yeast

Abstract

Dynamic disruption and reassembly of promoter-proximal nucleosomes is a conserved hallmark of transcriptionally active chromatin. Histone H3-K56 acetylation (H3K56Ac) enhances these turnover events and promotes nucleosome assembly during S phase. Here we sequence nascent transcripts to investigate the impact of H3K56Ac on transcription throughout the yeast cell cycle. We find that H3K56Ac is a genome-wide activator of transcription. While H3K56Ac has a major impact on transcription initiation, it also appears to promote elongation and/or termination. In contrast, H3K56Ac represses promiscuous transcription that occurs immediately following replication fork passage, in this case by promoting efficient nucleosome assembly. We also detect a stepwise increase in transcription as cells transit S phase and enter G2, but this response to increased gene dosage does not require H3K56Ac. Thus, a single histone mark can exert both positive and negative impacts on transcription that are coupled to different cell cycle events.

Transcription levels of a long noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast

“…During DNA replication in yeast, H3K56ac is directed to nucleosomes by chromatin assembly factors, perhaps they also play a role at IRT2 (Kaplan et al, 2008;Topal et al, 2019). Another possibility is that in the wake of transcription partial disassembly of nucleosomes leads to stochastic exchange of histones (Jamai et al, 2007).…”

“…In this regard, IRT2 transcription is perhaps the first event that directs H3K56ac to chromatin, subsequently H3K56ac can act in positive feedback to further increase nucleosome turnover. It is worth noting that H3K56ac is widespread at promoter proximal nucleosomes where divergent noncoding transcription takes place, which raises the interesting possibility that H3k56ac incorporation via noncoding transcription may be widespread (Topal et al, 2019;Xu et al, 2009).…”

The RNA-binding protein Puf5 buffers mRNA levels against chromatin-mediated changes in nascent transcription

“…Acetylation at this site is important to allow access to chromatin after DNA damage, enhance histone turnover at transcriptionally active chromatin, and to promote nucleosome assembly during S phase (Q. Li et al 2008;Kaplan et al 2008;Topal et al 2019;Wurtele et al 2012). Despite this important role in shaping chromatin, mutations at H3K56 to alanine or arginine only mildly affect the steady-state transcriptome (Topal et al 2019;Rege et al 2015).…”

“…Li et al 2008;Kaplan et al 2008;Topal et al 2019;Wurtele et al 2012). Despite this important role in shaping chromatin, mutations at H3K56 to alanine or arginine only mildly affect the steady-state transcriptome (Topal et al 2019;Rege et al 2015). Intriguingly though, genomewide nascent transcription is reduced in these mutants (Topal et al 2019), suggesting that post-transcriptional buffering of mRNA levels must exist.…”

“…Despite this important role in shaping chromatin, mutations at H3K56 to alanine or arginine only mildly affect the steady-state transcriptome (Topal et al 2019;Rege et al 2015). Intriguingly though, genomewide nascent transcription is reduced in these mutants (Topal et al 2019), suggesting that post-transcriptional buffering of mRNA levels must exist. Using a genome-wide genetic screen in Saccharomyces cerevisiae, we identify a puf5 mutant as synthetically lethal with H3K56A, indicating that Puf5 might work as a central player in this buffering system through its targeting of down-regulated nascent transcripts in an H3K56A background.…”