MYCN is recruited to the RASSF1A promoter but is not critical for DNA hypermethylation in neuroblastoma
Article first published online: 31 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
How to Cite
Charlet, J., Szemes, M., Malik, K. T.A. and Brown, K. W. (2012), MYCN is recruited to the RASSF1A promoter but is not critical for DNA hypermethylation in neuroblastoma. Mol. Carcinog.. doi: 10.1002/mc.21994
- Article first published online: 31 DEC 2012
- Manuscript Accepted: 28 NOV 2012
- Manuscript Revised: 9 NOV 2012
- Manuscript Received: 10 AUG 2012
- Fonds National de la Recherche (FNR) Luxembourg
- CLIC Sargent UK
- Kidney Research UK. Grant Number: RP42/2009
- University of Bristol Cancer Research Fund
- DNA hypermethylation
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.