Regional activation of the cancer genome by long-range epigenetic remodeling.
Cancer Cell, 2013/1/14;23(1):9-22.
Bert SA[1], Robinson MD, Strbenac D, Statham AL, Song JZ, Hulf T, Sutherland RL, Coolen MW, Stirzaker C, Clark SJ
Affiliations
PMID: 23245995
Impact factor: 38.585
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.
MeSH terms
Cell Line, Tumor; CpG Islands; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Genome; Histones; Humans; Male; MicroRNAs; Promoter Regions, Genetic; Prostatic Neoplasms
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