2010
DOI: 10.1038/cr.2010.128
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BRCA1 affects global DNA methylation through regulation of DNMT1

Abstract: Global DNA hypomethylation at CpG islands coupled with local hypermethylation is a hallmark for breast cancer, yet the mechanism underlying this change remains elusive. In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1.

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Cited by 90 publications
(61 citation statements)
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References 62 publications
(94 reference statements)
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“…S7). Moreover, DNA methyltransferase 1 (DNMT1) plays an important role in maintaining DNA methylation patterns [25,26], Shukla showed that DNMT1 was a transcriptional target of BRCA1 [27]. Our recent study confirmed that DNMT1 mRNA and protein were decreased in BRCA1 -mutated breast cancer.…”
Section: Discussionmentioning
confidence: 52%
“…S7). Moreover, DNA methyltransferase 1 (DNMT1) plays an important role in maintaining DNA methylation patterns [25,26], Shukla showed that DNMT1 was a transcriptional target of BRCA1 [27]. Our recent study confirmed that DNMT1 mRNA and protein were decreased in BRCA1 -mutated breast cancer.…”
Section: Discussionmentioning
confidence: 52%
“…Sears and colleagues also showed that HBP1 inhibits the activity of Myc, a gene often overexpressed in breast cancer (27). For this study, the decreases in HBP1 associated with breast and other cancers give a framework for the reports that DNMT1 levels increase in breast cancer (64)(65)(66). Our own inspection of the public databases further added the observation that reduced HBP1 levels were statistically associated with elevated DNMT1 levels ( Fig.…”
Section: Discussionmentioning
confidence: 92%
“…9 A recent study revealed that impaired function of BRCA1 leads to global DNA hypomethylation, loss of genomic imprinting, and an open chromatin configuration at premalignant stages of several types of tissues in a BRCA1 mutant mouse model and that in human clinical samples reduced expression of BRCA1 correlates with decreased levels of DNMT1 and reduced methylation of CpG islands. 40 Thus, BRCA1 dysfunction in BRACA1-associated hereditary breast cancers and sporadic basal-like breast cancers may be associated with lower methylation of CpG islands. 41,42 We found significantly higher methylation frequencies or levels in the promoter CpG islands of nine genes (APC, DLEC1, GSTP1, HOXA1, RASS-F1A, RUNX3, SCGB3A1, SFRP1, and TMEFF2) in the ER-positive group compared with the ERnegative group.…”
Section: Discussionmentioning
confidence: 99%