Regional Activation of the Cancer Genome by Long-Range Epigenetic Remodeling
Menée sur des lignées cellulaires, à l'aide de données d'expression de gènes et d'échantillons tumoraux prélevés sur des patients atteints d'un cancer de la prostate, cette étude met en évidence un mécanisme de régulation épigénétique à longue distance de gènes spécifiques du cancer
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. º We identify an epigenetic-based mechanism of regional cancer gene activation º Long-range epigenetic activation affects multiple adjacent tumor-associated genes º Regions are characterized by gain of active chromatin marks and loss of repressive marks º Promoter hypermethylation relates to cancer gene activation and changes in promoter usage
Cancer Cell 2013