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| Item Type: | Article |
|---|---|
| Title: | ELA2 is regulated by hematopoietic transcription factors, but not repressed by AML1-ETO |
| Creators Name: | Lausen, J., Liu, S., Fliegauf, M., Luebbert, M. and Werner, M.H. |
| Abstract: | A 117 bp fragment of the human ELA2 promoter has been characterized that can act as a minimal promoter for the expression of neutrophil elastase. Chromatin immunoprecipitation and siRNAs revealed that expression of ELA2 is regulated by the acute myeloid human leukemia 1 protein (AML1), C/EBPa, PU.1and c-Myb transcription factors. ELA2 has also been investigated as a possible target of the leukemic fusion protein AML1-ETO resulting from the t(8;21) chromosomal translocation. AML1-ETO, like AML1, binds the ELA2 promoter in the myeloid cell lines Kasumi-1and U937, but unexpectedly fails to significantly alter expression of ELA2. Although AML1-ETO downregulates the expression of C/EBPa, changes in C/EBPa expression do not correlate with changes in the expression of ELA2. Our observations indicate that AML1-ETO may not be a constitutive repressor of gene expression in every case in which it can associate with DNA, either on its own or in conjunction with C/EBPa. Since neither ETO nor AML1-ETO are typically expressed in hematopoietic progenitors, we hypothesize that it is the interactions between AML1- ETO and regulatory cofactors in disease-state cells that alter gene expression programs during hematopoiesis. These protein–protein interactions may not require simultaneous DNA binding by AML1-ETO for the deleterious effects of the fusion protein to be realized. |
| Keywords: | Acute Myeloid Leukemia, AML1-ETO, Gene Regulation, Neutrophil Elastase |
| Source: | Oncogene |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Volume: | 25 |
| Number: | 9 |
| Page Range: | 1349-1357 |
| Date: | 2 March 2006 |
| Official Publication: | https://doi.org/10.1038/sj.onc.1209181 |
| PubMed: | View item in PubMed |
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