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Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells

The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia

Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and member of the MYST family of histone acetyltransferases, is the target of recurrent translocations in acute myeloid leukemia. Since genes associated with translocations in leukemia are typically important regulators of blood formation, we investigated if Moz has a role in normal hematopoiesis. We generated mice carrying a mutation in the Moz gene. Homozygous Moz mutant mice died at birth. Moz mutant fetal liver hematopoietic cells were incapable of contributing to the hematopoietic system of recipients after transplantation. We observed profound defects in the stem cell compartment of Moz-deficient mice. Progenitors of all lineages were reduced in number. However, blood cell lineage commitment was unaffected. Together, these results show that Moz is essential for a fundamental property of hematopoietic stem cells, the ability to reconstitute the hematopoietic system of a recipient after transplantation and that Moz is specifically required in the stem cell compartment.

[Keywords: Monocytic leukemia zinc finger protein; histone acetyltransferase; hematopoiesis; stem cells]

Received October 7, 2005; revised version accepted February 24, 2006.

E-MAIL tthomas{at}wehi.edu.au; FAX 61-3-9347-0852.

² E-MAIL avoss{at}wehi.edu.au; FAX 61-3-9347-0852.

Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1382606

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