Title |
Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina–associated domains
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Published in |
Nature Genetics, November 2011
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DOI | 10.1038/ng.969 |
Pubmed ID | |
Authors |
Benjamin P Berman, Daniel J Weisenberger, Joseph F Aman, Toshinori Hinoue, Zachary Ramjan, Yaping Liu, Houtan Noushmehr, Christopher P E Lange, Cornelis M van Dijk, Rob A E M Tollenaar, David Van Den Berg, Peter W Laird |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 6 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 50% |
Scientists | 2 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 17 | 3% |
Germany | 4 | <1% |
Denmark | 3 | <1% |
Ireland | 2 | <1% |
Switzerland | 2 | <1% |
Belgium | 2 | <1% |
Spain | 2 | <1% |
Japan | 2 | <1% |
United Kingdom | 2 | <1% |
Other | 7 | 1% |
Unknown | 540 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 165 | 28% |
Researcher | 135 | 23% |
Student > Master | 60 | 10% |
Student > Bachelor | 38 | 7% |
Student > Doctoral Student | 33 | 6% |
Other | 94 | 16% |
Unknown | 58 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 236 | 40% |
Biochemistry, Genetics and Molecular Biology | 152 | 26% |
Medicine and Dentistry | 56 | 10% |
Computer Science | 14 | 2% |
Neuroscience | 8 | 1% |
Other | 43 | 7% |
Unknown | 74 | 13% |