MRC Laboratory for Molecular Cell Biology University College London, WC1E 6BT, London, UK.
Department of Biochemistry, University of Oxford, OX3 1QU, Oxford, UK.
Sci Rep. 2019 Jul 23;9(1):10686. doi: 10.1038/s41598-019-47170-z.
Activation of cell cycle regulated transcription during the G1-to-S transition initiates S phase entry and cell cycle commitment. The molecular mechanisms involving G1/S transcriptional regulation are well established and have been shown to be evolutionary conserved from yeast to humans. Previous work has suggested that changes to the chromatin state, specifically through histone acetylation, has an important role in the regulation of G1/S transcription in both yeast and human cells. Here we investigate the role of histone acetylation in G1/S transcriptional regulation in the budding yeast Saccharomyces cerevisiae. Our work shows that histone acetylation at specific sites at G1/S target gene promoters peaks at the G1-to-S transition, coinciding with their peak transcription levels. Acetylation at G1/S target promoters is significantly reduced upon deletion of the previously implicated histone acetyltransferase Gcn5, but G1/S cell cycle regulated transcription is largely unaffected. The histone deacetylase Rpd3, suggested to have a role in Whi5-dependent repression, is required for full repression of G1/S target genes in the G1 and S phases. However, in the context of transcriptionally active levels during the G1-to-S transition, this seems to play a minor role in the regulation of cell cycle transcription. Our data suggests that histone acetylation might modulate the amplitude of G1/S cell cycle regulated transcription in Saccharomyces cerevisiae, but has a limited role in its overall regulation.
细胞周期调控转录的激活在 G1 期到 S 期的转变过程中启动 S 期进入和细胞周期的启动。涉及 G1/S 转录调控的分子机制已经得到很好的建立，并已被证明从酵母到人是进化保守的。以前的工作表明，染色质状态的改变，特别是通过组蛋白乙酰化，在酵母和人类细胞中 G1/S 转录的调节中起着重要作用。在这里，我们研究了组蛋白乙酰化在芽殖酵母酿酒酵母 G1/S 转录调控中的作用。我们的工作表明，在 G1 期到 S 期的转变过程中，G1/S 靶基因启动子上的特定位点的组蛋白乙酰化达到峰值，与它们的转录水平峰值相吻合。在先前被认为参与组蛋白乙酰转移酶 Gcn5 的缺失时，G1/S 靶启动子上的乙酰化显著减少，但 G1/S 细胞周期调控转录则基本不受影响。组蛋白脱乙酰酶 Rpd3 被认为在 Whi5 依赖性抑制中起作用，在 G1 和 S 期，它对 G1/S 靶基因的完全抑制是必需的。然而，在 G1 期到 S 期的转录活性期间，它似乎在细胞周期转录的调节中只起次要作用。我们的数据表明，组蛋白乙酰化可能在酿酒酵母中调节 G1/S 细胞周期调控转录的幅度，但在其整体调控中作用有限。
