Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 May;53(5):413-20.
doi: 10.1002/mc.21994. Epub 2012 Dec 31.

MYCN Is Recruited to the RASSF1A Promoter but Is Not Critical for DNA Hypermethylation in Neuroblastoma

Affiliations

MYCN Is Recruited to the RASSF1A Promoter but Is Not Critical for DNA Hypermethylation in Neuroblastoma

Jessica Charlet et al. Mol Carcinog. .

Abstract

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.

Keywords: DNA hypermethylation; MYCN; epigenetics; neuroblastoma.

Similar articles

See all similar articles

Cited by 4 articles

Publication types

MeSH terms

Feedback