Regional activation of the cancer genome by long-range epigenetic remodeling
- PMID: 23245995
- DOI: 10.1016/j.ccr.2012.11.006
Regional activation of the cancer genome by long-range epigenetic remodeling
Abstract
Epigenetic gene deregulation in cancer commonly occurs through chromatin repression and promoter hypermethylation of tumor-associated genes. However, the mechanism underpinning epigenetic-based gene activation in carcinogenesis is still poorly understood. Here, we identify a mechanism of domain gene deregulation through coordinated long-range epigenetic activation (LREA) of regions that typically span 1 Mb and harbor key oncogenes, microRNAs, and cancer biomarker genes. Gene promoters within LREA domains are characterized by a gain of active chromatin marks and a loss of repressive marks. Notably, although promoter hypomethylation is uncommon, we show that extensive DNA hypermethylation of CpG islands or "CpG-island borders" is strongly related to cancer-specific gene activation or differential promoter usage. These findings have wide ramifications for cancer diagnosis, progression, and epigenetic-based gene therapies.
Copyright © 2013 Elsevier Inc. All rights reserved.
Comment in
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Epigenetic abnormalities in cancer find a "home on the range".Cancer Cell. 2013 Jan 14;23(1):1-3. doi: 10.1016/j.ccr.2012.12.018. Cancer Cell. 2013. PMID: 23328477 Free PMC article.
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Epigenetics: the long view.Nat Rev Cancer. 2013 Feb;13(2):76. doi: 10.1038/nrc3454. Epub 2013 Jan 18. Nat Rev Cancer. 2013. PMID: 23329064 No abstract available.
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