Regional Activation of the Cancer Genome by Long-Range Epigenetic Remodeling
- Author(s)
- Bert, SA; Robinson, MD; Strbenac, D; Statham, AL; Song, JZ; Hulf, T; Sutherland, RL; Coolen, MW; Stirzaker, C; Clark, SJ;
- Details
- Publication Year 2013-01-14,Volume 23,Issue #1,Page 9-22
- Journal Title
- CANCER CELL
- Publication Type
- Journal Article
- 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.
- Publisher
- CELL PRESS
- Keywords
- CPG ISLAND SHORES; DNA METHYLATION; PROSTATE-CANCER; REPRESSIVE CHROMATIN; GENE FUSIONS; STEM-CELLS; HYPOMETHYLATION; HYPERMETHYLATION; IDENTIFICATION; SEQUENCES
- Research Division(s)
- Bioinformatics
- Publisher's Version
- https://doi.org/10.1016/j.ccr.2012.11.006
- Terms of Use/Rights Notice
- Copyright © 2013 Elsevier Inc. All rights reserved.
Creation Date: 2013-01-14 12:00:00