Regional Activation of the Cancer Genome by Long-Range Epigenetic Remodeling
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
Terms of Use/Rights Notice
Copyright © 2013 Elsevier Inc. All rights reserved.


Creation Date: 2013-01-14 12:00:00
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