Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research
Author(s)
Shenker, N
Flanagan, JM
Type
Journal Article
Abstract
Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation.
Date Issued
2011-12-13
Date Acceptance
2011-11-24
Citation
British Journal of Cancer, 2011, 106 (2), pp.248-253
ISSN
1532-1827
Publisher
Cancer Research UK
Start Page
248
End Page
253
Journal / Book Title
British Journal of Cancer
Volume
106
Issue
2
Copyright Statement
This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.
Sponsor
Breast Cancer Now
Grant Number
2009MaySF03
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
ONCOLOGY
epigenetics
DNA methylation
breast cancer
intragenic
gene-body
BODY-SPECIFIC METHYLATION
HUMAN-CELLS
CPG-ISLANDS
GENOME
WIDE
TRANSCRIPTION
GENES
LANDSCAPES
PROMOTERS
REGIONS
Animals
DNA Methylation
Epigenesis, Genetic
Humans
Neoplasms
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status
Published