Title |
Homeobox oncogene activation by pan-cancer DNA hypermethylation
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Published in |
Genome Biology, August 2018
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DOI | 10.1186/s13059-018-1492-3 |
Pubmed ID | |
Authors |
Jianzhong Su, Yung-Hsin Huang, Xiaodong Cui, Xinyu Wang, Xiaotian Zhang, Yong Lei, Jianfeng Xu, Xueqiu Lin, Kaifu Chen, Jie Lv, Margaret A. Goodell, Wei Li |
Abstract |
Cancers have long been recognized to be not only genetically but also epigenetically distinct from their tissues of origin. Although genetic alterations underlying oncogene upregulation have been well studied, to what extent epigenetic mechanisms, such as DNA methylation, can also induce oncogene expression remains unknown. Here, through pan-cancer analysis of 4174 genome-wide profiles, including whole-genome bisulfite sequencing data from 30 normal tissues and 35 solid tumors, we discover a strong correlation between gene-body hypermethylation of DNA methylation canyons, defined as broad under-methylated regions, and overexpression of approximately 43% of homeobox genes, many of which are also oncogenes. To gain insights into the cause-and-effect relationship, we use a newly developed dCas9-SunTag-DNMT3A system to methylate genomic sites of interest. The locus-specific hypermethylation of gene-body canyon, but not promoter, of homeobox oncogene DLX1, can directly increase its gene expression. Our pan-cancer analysis followed by functional validation reveals DNA hypermethylation as a novel epigenetic mechanism for homeobox oncogene upregulation. |
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Geographical breakdown
Country | Count | As % |
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United States | 7 | 47% |
Australia | 1 | 7% |
Mexico | 1 | 7% |
Singapore | 1 | 7% |
United Kingdom | 1 | 7% |
Unknown | 4 | 27% |
Demographic breakdown
Type | Count | As % |
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Scientists | 7 | 47% |
Members of the public | 5 | 33% |
Science communicators (journalists, bloggers, editors) | 2 | 13% |
Practitioners (doctors, other healthcare professionals) | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 96 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 18 | 19% |
Researcher | 15 | 16% |
Student > Master | 10 | 10% |
Student > Bachelor | 6 | 6% |
Professor > Associate Professor | 5 | 5% |
Other | 12 | 13% |
Unknown | 30 | 31% |
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Biochemistry, Genetics and Molecular Biology | 34 | 35% |
Agricultural and Biological Sciences | 18 | 19% |
Medicine and Dentistry | 4 | 4% |
Unspecified | 2 | 2% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 1% |
Other | 4 | 4% |
Unknown | 33 | 34% |