Abstract |
The oncogene BMI1 encodes a polycomb group transcription factor that is required for embryonic development and self-renewal of stem cells. Despite these important functions little is known about the regulation of BMI1 expression. A cDNA microarray based search for target genes of E2F-1 in neuroblastoma cells expressing a 4-OHT-regulated E2F-1-ER fusion protein identified many hitherto unknown E2F-1 regulated genes. A total of 10% of these genes, including BMI1, encode proteins that function primarily in the regulation of gene expression. The BMI1 promoter contains a putative E2F binding site that was required for the activation of a BMI1 promoter-dependent reporter construct by E2F-1. Chromatin immunoprecipitation revealed 4-OHT-dependent binding of E2F-1-ER and binding of endogenous E2F-1 to the BMI1 promoter in tumor cells. We have previously shown activation of the oncogene MYCN by E2F. Thus, in neuroblastomas deregulated E2F-1 can activate two oncogenes, MYCN and BMI1 that are known to co-operate in tumor formation. Consistent with a role of Bmi1 in neuroblastoma tumorigenesis we found strong Bmi1 expression in primary neuroblastomas. Our results reveal a novel link between E2F and polycomb transcription factors and suggest a role of Bmi1 in neuroblastomas.
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Authors | Katrin Nowak, Kornelius Kerl, Daniel Fehr, Christoph Kramps, Christine Gessner, Katrin Killmer, Birgit Samans, Bernd Berwanger, Holger Christiansen, Werner Lutz |
Journal | Nucleic acids research
(Nucleic Acids Res)
Vol. 34
Issue 6
Pg. 1745-54
( 2006)
ISSN: 1362-4962 [Electronic] England |
PMID | 16582100
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BMI1 protein, human
- Chromatin
- E2F1 Transcription Factor
- Nuclear Proteins
- Proto-Oncogene Proteins
- Repressor Proteins
- Polycomb Repressive Complex 1
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Topics |
- Animals
- Binding Sites
- Cell Cycle
- Cell Differentiation
- Cell Line, Tumor
- Cells, Cultured
- Chromatin
(metabolism)
- E2F1 Transcription Factor
(metabolism)
- Gene Expression Regulation, Neoplastic
- Humans
- Mice
- Nervous System Neoplasms
(genetics, metabolism)
- Neuroblastoma
(genetics, metabolism)
- Nuclear Proteins
(genetics, metabolism)
- Polycomb Repressive Complex 1
- Promoter Regions, Genetic
- Proto-Oncogene Proteins
(genetics, metabolism)
- Repressor Proteins
(genetics, metabolism)
- Tumor Cells, Cultured
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