Type

Journal Article

Authors

Raymond L Stallings
Kenneth Bryan
Karen M Watters
Sudipto Das
Patrick G Buckley
Derek M Murphy

Subjects

Biochemistry

Topics
mycn protein human binding sites genome human dna binding proteins protein transport metabolism humans e box elements cpg islands methyl cpg binding protein 2 dna female protein binding nuclear proteins genetics signal transduction cell line tumor neuroblastoma transcription factors computational biology dna methylation hemizygote gene expression regulation neoplastic mecp2 protein human oncogene proteins

Co-localization of the oncogenic transcription factor MYCN and the DNA methyl binding protein MeCP2 at genomic sites in neuroblastoma. (2011)

Abstract MYCN is a transcription factor that is expressed during the development of the neural crest and its dysregulation plays a major role in the pathogenesis of pediatric cancers such as neuroblastoma, medulloblastoma and rhabdomyosarcoma. MeCP2 is a CpG methyl binding protein which has been associated with a number of cancers and developmental disorders, particularly Rett syndrome. Using an integrative global genomics approach involving chromatin immunoprecipitation applied to microarrays, we have determined that MYCN and MeCP2 co-localize to gene promoter regions, as well as inter/intragenic sites, within the neuroblastoma genome (MYCN amplified Kelly cells) at high frequency (70.2% of MYCN sites were also positive for MeCP2). Intriguingly, the frequency of co-localization was significantly less at promoter regions exhibiting substantial hypermethylation (8.7%), as determined by methylated DNA immunoprecipitation (MeDIP) applied to the same microarrays. Co-immunoprecipitation of MYCN using an anti-MeCP2 antibody indicated that a MYCN/MeCP2 interaction occurs at protein level. mRNA expression profiling revealed that the median expression of genes with promoters bound by MYCN was significantly higher than for genes bound by MeCP2, and that genes bound by both proteins had intermediate expression. Pathway analysis was carried out for genes bound by MYCN, MeCP2 or MYCN/MeCP2, revealing higher order functions. Our results indicate that MYCN and MeCP2 protein interact and co-localize to similar genomic sites at very high frequency, and that the patterns of binding of these proteins can be associated with significant differences in transcriptional activity. Although it is not yet known if this interaction contributes to neuroblastoma disease pathogenesis, it is intriguing that the interaction occurs at the promoter regions of several genes important for the development of neuroblastoma, including ALK, AURKA and BDNF.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Raymond L Stallings, Kenneth Bryan, Karen M Watters, Sudipto Das, Patrick G Buckley, Derek M Murphy

Experts in our system

1
Raymond L Stallings
Royal College of Surgeons in Ireland
Total Publications: 59
 
2
Kenneth Bryan
Royal College of Surgeons in Ireland
Total Publications: 36
 
3
Sudipto Das
Royal College of Surgeons in Ireland
Total Publications: 15