Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA, 01605, USA.
Institut de Génétique Moléculaire de Montpellier, UMR 5535 CNRS, 1919 Route de Mende, 34293, Montpellier Cedex 5, France.
Nat Commun. 2019 Sep 26;10(1):4372. doi: 10.1038/s41467-019-12400-5.
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.
动态破坏和重新组装启动子近端核小体是转录活性染色质的一个保守特征。组蛋白 H3-K56 乙酰化(H3K56Ac)增强了这些周转事件,并在 S 期促进核小体组装。在这里,我们对新生转录本进行测序,以研究 H3K56Ac 对整个酵母细胞周期转录的影响。我们发现 H3K56Ac 是全基因组转录的激活剂。虽然 H3K56Ac 对转录起始有重大影响,但它似乎也促进了延伸和/或终止。相比之下,H3K56Ac 抑制复制叉通过后立即发生的混杂转录,在这种情况下,通过促进有效的核小体组装来实现。我们还检测到随着细胞进入 S 期和 G2 期,转录逐渐增加,但这种对基因剂量增加的反应并不需要 H3K56Ac。因此,单个组蛋白标记可以对转录产生正反两方面的影响,这些影响与不同的细胞周期事件相关。