COMPASS 复合物对 H3K4me3 的识别有助于在 DNA 复制后恢复这种组蛋白标记。
H3K4me3 recognition by the COMPASS complex facilitates the restoration of this histone mark following DNA replication.
机构信息
Institute for Cancer Genetics, Department of Pediatrics and Department of Genetics and Development, Columbia University Irving Medical Center, New York, NY 10032, USA.
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
出版信息
Sci Adv. 2022 May 6;8(18):eabm6246. doi: 10.1126/sciadv.abm6246.
During DNA replication, parental H3-H4 marked by H3K4me3 are transferred almost equally onto leading and lagging strands of DNA replication forks. Mutations in replicative helicase subunit, Mcm2 (Mcm2-3A), and leading strand DNA polymerase subunit, Dpb3 (∆), result in asymmetric distributions of H3K4me3 at replicating DNA strands immediately following DNA replication. Here, we show that and ∆ mutant cells markedly reduce the asymmetric distribution of H3K4me3 during cell cycle progression before mitosis. Furthermore, the restoration of a more symmetric distribution of H3K4me3 at replicating DNA strands in these mutant cells is driven by methylating nucleosomes without H3K4me3 by the H3K4 methyltransferase complex, COMPASS. Last, both gene transcription machinery and the binding of parental H3K4me3 by Spp1 subunit of the COMPASS complex help recruit the enzyme to chromatin for the restoration of the H3K4me3-marked state following DNA replication, shedding light on inheritance of this mark following DNA replication.
在 DNA 复制过程中，被 H3K4me3 标记的亲本 H3-H4 几乎平等地转移到 DNA 复制叉的前导链和滞后链上。复制酶亚基 Mcm2（Mcm2-3A）和前导链 DNA 聚合酶亚基 Dpb3（∆）的突变导致 DNA 复制后，复制 DNA 链上 H3K4me3 的不对称分布。在这里，我们发现 和 ∆ 突变细胞在有丝分裂前的细胞周期进程中明显减少了 H3K4me3 的不对称分布。此外，这些突变细胞中复制 DNA 链上 H3K4me3 分布更为对称的恢复是由 H3K4 甲基转移酶复合物 COMPASS 驱动的，该复合物可以对没有 H3K4me3 的核小体进行甲基化。最后，基因转录机制和 COMPASS 复合物中亲本 H3K4me3 的 Spp1 亚基的结合有助于将酶募集到染色质上，以恢复 DNA 复制后的 H3K4me3 标记状态，为 DNA 复制后该标记的遗传提供了线索。
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