MYCN is recruited to the RASSF1A promoter but is not critical for DNA hypermethylation in neuroblastoma

Jessica Charlet, Marianna Szemes, Karim T A Malik, Keith W Brown

Research output: Contribution to journalArticle (Academic Journal)peer-review

6 Citations (Scopus)

Abstract

Tumour 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 tumour 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.
Original languageEnglish
Pages (from-to)413-420
Number of pages8
JournalMolecular Carcinogenesis
Volume53
Issue number5
Early online date31 Dec 2012
DOIs
Publication statusPublished - May 2014

Keywords

  • MYCN, epigenetics, neuroblastoma, DNA hypermethylation

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