MOZ is essential for maintenance of hematopoietic stem cells.

Monocytic leukemia zinc-finger protein (MOZ), a MYST family histone acetyltransferase, is involved in the chromosome translocations associated with acute myeloid leukemia. MOZ acts as a transcriptional coactivator for AML1, which is essential for establishment of definitive hematopoiesis. To investigate the roles of MOZ in normal hematopoiesis, we generated MOZ-null mice. ...
MOZ-/- mice died around embryonic day 15 (E15). In MOZ-/- E14.5 embryos, hematopoietic stem cells, lineage-committed progenitors, and B lineage cells were severely reduced. On the other hand, arrest of erythroid maturation and elevated myeloid lineage populations were observed. MOZ-deficient fetal liver cells could not reconstitute hematopoiesis of recipients after transplantation. Analysis using microarray and flow cytometry revealed that expression of thrombopoietin receptor (c-Mpl), HoxA9, and c-Kit was down-regulated. These results show that MOZ is required for maintenance of hematopoietic stem cells, and that it plays a role in differentiation of erythroid and myeloid cells. Some aspects of the MOZ-/- phenotype are similar to that observed in PU.1-deficient mice. MOZ was able to interact with PU.1 and activate PU.1-dependent transcription, thus suggesting a physical and functional link between PU.1 and MOZ.
Mesh Terms:
Animals, B-Lymphocytes, Cell Differentiation, Cell Lineage, Down-Regulation, Embryonic Development, Erythropoiesis, Gene Expression Regulation, Developmental, Genes, Lethal, Hematopoietic Stem Cells, Histone Acetyltransferases, Homeodomain Proteins, Leukemia, Liver, Mice, Mice, Mutant Strains, Myelopoiesis, Oncogene Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-kit, Receptors, Cytokine, Receptors, Thrombopoietin, Trans-Activators, Transcriptional Activation
Genes Dev.
Date: May. 15, 2006
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