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

• Published in: Oncogene Vol. 25; no. 9; pp. 1349 - 1357
• Main Authors: LAUSEN, J, LIU, S, FLIEGAUF, M, LÜBBERT, M, WERNER, M. H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 02-03-2006; Nature Publishing Group
• Subjects: Acute Disease; AML1 protein; Biological and medical sciences; Biophysics; c-Myb protein; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromatin; Chromatin Immunoprecipitation; Chromosome translocations; Cofactors; Core Binding Factor Alpha 2 Subunit - physiology; Deoxyribonucleic acid; DNA; DNA-Binding Proteins; Elastase; Fundamental and applied biological sciences. Psychology; Fusion protein; Gene expression; Gene Expression Regulation, Neoplastic; Hematopoiesis - genetics; Hemopoiesis; Humans; Immunoprecipitation; Kinases; Leukemia; Leukemia, Myeloid - genetics; Leukocytes (neutrophilic); Molecular and cellular biology; Mutation; Neutropenia; Neutrophils; Oncogene Proteins, Fusion - physiology; Progenitor cells; Promoter Regions, Genetic; Protein interaction; Proteins; PU.1 protein; RNA, Small Interfering; RUNX1 Translocation Partner 1 Protein; Serine Endopeptidases - biosynthesis; Serine Endopeptidases - genetics; siRNA; Transcription factors; Transcription Factors - physiology; New York; United States > US; AML1-ETO; acute myeloid leukemia; Hematopoiesis; gene regulation; neutrophil elastase; Repression; Transcription factor; Carcinogenesis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1209181

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/EBPalpha, 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/EBPalpha, changes in C/EBPalpha 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/EBPalpha. 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.