Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma

Bunt, Jens, Hasselt, Nancy E., Zwijnenburg, Danny A., Koster, Jan, Versteeg, Rogier and Kool, Marcel (2011) Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma. PloS One, 6 10: e26058.1-e26058.9. doi:10.1371/journal.pone.0026058


Author Bunt, Jens
Hasselt, Nancy E.
Zwijnenburg, Danny A.
Koster, Jan
Versteeg, Rogier
Kool, Marcel
Title Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-10-10
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pone.0026058
Open Access Status DOI
Volume 6
Issue 10
Start page e26058.1
End page e26058.9
Total pages 10
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2012
Language eng
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
Abstract Both OTX2 and MYC are important oncogenes in medulloblastoma, the most common malignant brain tumor in childhood. Much is known about MYC binding to promoter regions, but OTX2 binding is hardly investigated. We used ChIP-on-chip data to analyze the binding patterns of both transcription factors in D425 medulloblastoma cells. When combining the data for all promoter regions in the genome, OTX2 binding showed a remarkable bi-modal distribution pattern with peaks around -250 bp upstream and +650 bp downstream of the transcription start sites (TSSs). Indeed, 40.2% of all OTX2-bound TSSs had more than one significant OTX2-binding peak. This OTX2-binding pattern was very different from the TSS-centered single peak binding pattern observed for MYC and other known transcription factors. However, in individual promoter regions, OTX2 and MYC have a strong tendency to bind in proximity of each other. OTX2-binding sequences are depleted near TSSs in the genome, providing an explanation for the observed bi-modal distribution of OTX2 binding. This contrasts to the enrichment of E-box sequences at TSSs. Both OTX2 and MYC binding independently correlated with higher gene expression. Interestingly, genes of promoter regions with multiple OTX2 binding as well as MYC binding showed the highest expression levels in D425 cells and in primary medulloblastomas. Genes within this class of promoter regions were enriched for medulloblastoma and stem cell specific genes. Our data suggest an important functional interaction between OTX2 and MYC in regulating gene expression in medulloblastoma.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Sun, 23 Feb 2014, 15:52:23 EST by Jens Bunt on behalf of Queensland Brain Institute