Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains.
Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains.
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DNA甲基化的广泛变化在癌症中是常见的，并且可能通过肿瘤抑制基因的转录沉默而促成肿瘤发生。基因组规模的研究已经对这些变化产生了重要的见解，但主要集中在CpG岛或基因启动子上。我们使用全基因组亚硫酸氢盐测序（bisulfite-seq）以单碱基对分辨率全面分析原发性人类结直肠肿瘤和邻近正常结肠组织。肿瘤中的局灶性高甲基化区域主要位于CpG岛，并集中在长距离（>100 kb）低甲基化区域内。这些低甲基化的结构域覆盖了近一半的基因组，并与人类细胞系中晚期复制和附着到核纤层相一致。我们证实了在25个不同的结直肠肿瘤和匹配的邻近组织中这些区域的高甲基化和低甲基化的汇合。我们认为，癌症中广泛的DNA甲基化变化与细胞核内染色质三维组织协调的沉默程序有关。
Extensive changes in DNA methylation are common in cancer and may contribute to oncogenesis through transcriptional silencing of tumor-suppressor genes. Genome-scale studies have yielded important insights into these changes but have focused on CpG islands or gene promoters. We used whole-genome bisulfite sequencing (bisulfite-seq) to comprehensively profile a primary human colorectal tumor and adjacent normal colon tissue at single-basepair resolution. Regions of focal hypermethylation in the tumor were located primarily at CpG islands and were concentrated within regions of long-range (>100 kb) hypomethylation. These hypomethylated domains covered nearly half of the genome and coincided with late replication and attachment to the nuclear lamina in human cell lines. We confirmed the confluence of hypermethylation and hypomethylation within these domains in 25 diverse colorectal tumors and matched adjacent tissue. We propose that widespread DNA methylation changes in cancer are linked to silencing programs orchestrated by the three-dimensional organization of chromatin within the nucleus.
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影响因子：
9.8
作者：
ENCODE Project Consortium
通讯作者：
ENCODE Project Consortium
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
4.5
作者：
Boumber YA;Kondo Y;Chen X;Shen L;Guo Y;Tellez C;Estécio MR;Ahmed S;Issa JP
通讯作者：
Issa JP
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
7
作者：
Cuddapah, Suresh;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji