Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells

Dasse E, Volpe G, Walton DS, Wilson N, Del Pozzo W, O'Neill LP, Slany R, Frampton J, Dumon S (2012)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2012

Journal

Blood Cancer Journal Nature Publishing Group / Nature Publishing Group: Open Access Journals - Option B

Book Volume: 2

Article Number: e76

Journal Issue: 6

DOI: 10.1038/bcj.2012.20

Abstract

The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells. © 2012 Macmillan Publishers Limited All rights reserved.

Authors with CRIS profile

Robert Slany Lehrstuhl für Genetik

Involved external institutions

University of Birmingham GB United Kingdom (GB) National Institute for Subatomic Physics / Nationaal instituut voor subatomaire fysica (Nikhef) NL Netherlands (NL) University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Dasse, E., Volpe, G., Walton, D.S., Wilson, N., Del Pozzo, W., O'Neill, L.P.,... Dumon, S. (2012). Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells. Blood Cancer Journal, 2(6). https://doi.org/10.1038/bcj.2012.20

MLA:

Dasse, E., et al. "Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells." Blood Cancer Journal 2.6 (2012).

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