Document Detail


MYCN is recruited to the RASSF1A promoter but is not critical for DNA hypermethylation in neuroblastoma.
MedLine Citation:
PMID:  23280764     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tumor suppressor genes such as RASSF1A are often epigenetically repressed by DNA hypermethylation in neuroblastoma, where the MYCN proto-oncogene is frequently amplified. MYC has been shown to associate with DNA methyltransferases, thereby inducing transcriptional repression of target genes, which suggested that MYCN might play a similar mechanistic role in the hypermethylation of tumor suppressor genes in neuroblastoma. This study tested that hypothesis by using co-immunoprecipitation and ChIP to investigate MYCN-DNA methyltransferase interactions, together with MYCN knock-down and over-expression systems to examine the effect of MYCN expression changes on gene methylation, employing both candidate gene and genome-wide assays. We show that MYCN interacts with DNA methyltransferases and is recruited to the promoter region of RASSF1A. However, using four model systems, we showed that long-term silencing of MYCN induces only a small loss of DNA methylation at the RASSF1A promoter in MYCN amplified neuroblastoma cell lines and over-expression of MYCN does not induce any DNA methylation, suggesting that MYCN is not critical for DNA hypermethylation in neuroblastoma. © 2012 Wiley Periodicals, Inc.
Authors:
Jessica Charlet; Marianna Szemes; Karim T A Malik; Keith W Brown
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-31
Journal Detail:
Title:  Molecular carcinogenesis     Volume:  -     ISSN:  1098-2744     ISO Abbreviation:  Mol. Carcinog.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-1-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8811105     Medline TA:  Mol Carcinog     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
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