DNA methylation loss in late-replicating domains is linked to mitotic cell division.
DNA methylation loss in late-replicating domains is linked to mitotic cell division.
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DOI：
10.1038/s41588-018-0073-4
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发表时间：
2018-04
期刊：
影响因子：
30.8
通讯作者：
Berman BP
中科院分区：
文献类型：
--
作者：
Zhou W;Dinh HQ;Ramjan Z;Weisenberger DJ;Nicolet CM;Shen H;Laird PW;Berman BP
DNA甲基化丢失经常发生在癌症基因组中，主要在被称为部分甲基化结构域（PMD）的核纤层相关的晚期复制区域内。我们使用全基因组亚硫酸氢盐测序（WGBS）分析了39种不同的原发性肿瘤和8种匹配的邻近组织，并与343个额外的人类和206个小鼠WGBS数据集一起分析了它们。我们确定了一个本地的CpG序列上下文与优先低甲基化PMD。在这种情况下的CpG分析（“Solo-WCGW”）揭示了几乎所有健康组织类型中先前未检测到的PMD低甲基化。PMD低甲基化随着年龄的增长而增加，在胎儿发育期间开始，并出现跟踪细胞分裂的积累。在癌症中，PMD低甲基化深度与体细胞突变密度和细胞周期基因表达相关，与其有丝分裂历史的反映一致，并表明其作为有丝分裂时钟的应用。我们认为，晚期复制导致终身进行性甲基化丢失，这是细胞衰老的生物标志物，可能有助于肿瘤发生。
DNA methylation loss occurs frequently in cancer genomes, primarily within lamina-associated, late-replicating regions termed Partially Methylated Domains (PMDs). We profiled 39 diverse primary tumors and 8 matched adjacent tissues using Whole-Genome Bisulfite Sequencing (WGBS), and analyzed them alongside 343 additional human and 206 mouse WGBS datasets. We identified a local CpG sequence context associated with preferential hypomethylation in PMDs. Analysis of CpGs in this context (“Solo-WCGWs”) revealed previously undetected PMD hypomethylation in almost all healthy tissue types. PMD hypomethylation increased with age, beginning during fetal development, and appeared to track the accumulation of cell divisions. In cancer, PMD hypomethylation depth correlated with somatic mutation density and cell-cycle gene expression, consistent with its reflection of mitotic history, and suggesting its application as a mitotic clock. We propose that late replication leads to lifelong progressive methylation loss, which acts as a biomarker for cellular aging and which may contribute to oncogenesis.
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影响因子：
12.3
作者：
Fortin JP;Hansen KD
通讯作者：
Hansen KD
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
14.9
作者：
EHRLICH, M;GAMASOSA, MA;GEHRKE, C
通讯作者：
GEHRKE, C
影响因子：
56.9
作者：
GOELZ, SE;VOGELSTEIN, B;FEINBERG, AP
通讯作者：
FEINBERG, AP