Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction.

Abstract:

:Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. The specificity is influenced by genome architecture and epigenetic factors, but their relationship is still unknown. In this study, we isolated promoter CGIs susceptible and resistant to aberrant methylation induction during prostate and breast carcinogenesis. The effect of genome architecture was more evident for promoter CGIs susceptible in both of the two tissues than for promoter CGIs susceptible only in one tissue. Multivariate analysis of promoter CGIs with tissue-nonspecific susceptibility showed that genome architecture, namely a remote location from SINE (OR=5.98; 95% CI=2.33-15.34) and from LINE (OR=2.08; 95% CI=1.03-4.21), was associated with increased susceptibility, independent of epigenetic factors such as the presence of RNA polymerase II (OR=0.09; 95% CI=0.02-0.48) and H3K27me3 (OR=3.28; 95% CI=1.17-9.21). These results showed that methylation susceptibility of promoter CGIs is determined both by genome architecture and epigenetic factors, independently.

journal_name

Genomics

journal_title

Genomics

authors

Takeshima H,Yamashita S,Shimazu T,Ushijima T

doi

10.1016/j.ygeno.2011.06.003

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

182-8

issue

3

eissn

0888-7543

issn

1089-8646

pii

S0888-7543(11)00140-6

journal_volume

98

pub_type

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