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  • Original Article
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ELA2 is regulated by hematopoietic transcription factors, but not repressed by AML1-ETO

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/EBPα, PU.1 and 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-1 and U937, but unexpectedly fails to significantly alter expression of ELA2. Although AML1-ETO downregulates the expression of C/EBPα, changes in C/EBPα 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/EBPα. 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.

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Acknowledgements

This work was supported in part by a fellowship from the Deutsche Forschungsgemeinschaft (LA 1389/1-1) (to JL) and by the Specialized Center for Research Grant from the Leukemia and Lymphoma Society (to MHW). MHW is a Distinguished Young Scholar of the W M Keck Foundation. We thank S Hiebert, N Timchenko, EP Reddy, MJ Klemsz and S Nimer for providing expression and reporter vectors and T Berg and M Lübbert for sharing AML1-ETO microarray data prior to publication. ML is supported by the German José Carreras Foundation (00/14).

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Correspondence to M H Werner.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Lausen, J., Liu, S., Fliegauf, M. et al. ELA2 is regulated by hematopoietic transcription factors, but not repressed by AML1-ETO. Oncogene 25, 1349–1357 (2006). https://doi.org/10.1038/sj.onc.1209181

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