The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
The Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), 41092 Sevilla, Spain.
Mol Cell. 2021 Jul 1;81(13):2793-2807.e8. doi: 10.1016/j.molcel.2021.04.021. Epub 2021 May 11.
DNA replication initiates at genomic locations known as origins of replication, which, in S. cerevisiae, share a common DNA consensus motif. Despite being virtually nucleosome-free, origins of replication are greatly influenced by the surrounding chromatin state. Here, we show that histone H3 lysine 37 mono-methylation (H3K37me1) is catalyzed by Set1p and Set2p and that it regulates replication origin licensing. H3K37me1 is uniformly distributed throughout most of the genome, but it is scarce at replication origins, where it increases according to the timing of their firing. We find that H3K37me1 hinders Mcm2 interaction with chromatin, maintaining low levels of MCM outside of conventional replication origins. Lack of H3K37me1 results in defective DNA replication from canonical origins while promoting replication events at inefficient and non-canonical sites. Collectively, our results indicate that H3K37me1 ensures correct execution of the DNA replication program by protecting the genome from inappropriate origin licensing and spurious DNA replication.
DNA 复制起始于称为复制起点的基因组位置，在酿酒酵母中，这些复制起点具有共同的 DNA 共识基序。尽管实际上无核小体，但复制起点受周围染色质状态的极大影响。在这里，我们表明组蛋白 H3 赖氨酸 37 单甲基化 (H3K37me1) 由 Set1p 和 Set2p 催化，并调节复制起点许可。H3K37me1 在基因组的大部分区域均匀分布，但在复制起点处很少，在复制起点处，根据其启动时间增加。我们发现 H3K37me1 阻碍 Mcm2 与染色质的相互作用，从而在传统复制起点之外保持低水平的 MCM。缺乏 H3K37me1 会导致来自规范起点的 DNA 复制缺陷，同时促进低效和非规范位点的复制事件。总的来说，我们的结果表明 H3K37me1 通过防止基因组不适当的起点许可和虚假的 DNA 复制，确保 DNA 复制程序的正确执行。
