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Regional activation of the cancer genome by long-range epigenetic remodeling


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.

Type Journal
Authors Bert, S.A.; Robinson, M.D.; Strbenac, D.; Statham, A.L.; Song, J.Z.; Hulf, T.; Sutherland, R.L.; Coolen, M.W.; Stirzaker, C.; Clark, S.J.
Publisher Name CANCER CELL
Published Date 2013-01-01
Published Volume 23
Published Issue 1
Published Pages 9-22
Status Published in-print
DOI 10.1016/j.ccr.2012.11.006
URL link to publisher's version
OpenAccess link to author's accepted manuscript version