دورية أكاديمية
Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma.
| العنوان: | Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma. |
|---|---|
| المؤلفون: | Bunt J; Department of Oncogenomics, Academic Medical Center, Amsterdam, The Netherlands., Hasselt NE, Zwijnenburg DA, Koster J, Versteeg R, Kool M |
| المصدر: | PloS one [PLoS One] 2011; Vol. 6 (10), pp. e26058. Date of Electronic Publication: 2011 Oct 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
| مواضيع طبية MeSH: | Cerebellar Neoplasms/*pathology , Gene Expression Regulation, Neoplastic/*genetics , Medulloblastoma/*pathology , Otx Transcription Factors/*metabolism , Promoter Regions, Genetic/*genetics , Proto-Oncogene Proteins c-myc/*metabolism, Cell Line, Tumor ; Cerebellar Neoplasms/genetics ; DNA/genetics ; DNA/metabolism ; Humans ; Medulloblastoma/genetics ; Nucleotide Motifs/genetics ; Protein Binding ; Stem Cells/metabolism ; Substrate Specificity ; Transcription Initiation Site |
| مستخلص: | 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. |
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| المشرفين على المادة: | 0 (MYC protein, human) 0 (OTX2 protein, human) 0 (Otx Transcription Factors) 0 (Proto-Oncogene Proteins c-myc) 9007-49-2 (DNA) |
| تواريخ الأحداث: | Date Created: 20111022 Date Completed: 20120213 Latest Revision: 20211020 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3189962 |
| DOI: | 10.1371/journal.pone.0026058 |
| PMID: | 22016811 |
| قاعدة البيانات: | MEDLINE |
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