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.

• Authors: Saul A Bert, Mark D Robinson, Dario Strbenac, Aaron L Statham, Jenny Z Song, Toby Hulf, Robert L Sutherland, Marcel W Coolen, Clare Stirzaker, Susan J Clark
• Journal: Cancer cell (Cancer Cell) Vol. 23 Issue 1 Pg. 9-22 (Jan 14 2013) ISSN: 1878-3686 [Electronic] United States
• PMID: 23245995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Histones
• MicroRNAs

Topics

• Cell Line, Tumor
• CpG Islands
• DNA Methylation
• Epigenesis, Genetic
• Gene Expression Regulation, Neoplastic
• Genome
• Histones (metabolism)
• Humans
• Male
• MicroRNAs (genetics, physiology)
• Promoter Regions, Genetic
• Prostatic Neoplasms (genetics)