MOZ is essential for maintenance of hematopoietic stem cells
MOZ is essential for maintenance of hematopoietic stem cells
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DOI：
10.1101/gad.1393106
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发表时间：
2006-05-15
影响因子：
10.5
通讯作者：
Kitabayashi, Issay
中科院分区：
文献类型：
--
作者：
Katsumoto, Takuo;Aikawa, Yukiko;Kitabayashi, Issay
单核细胞白血病锌指蛋白（MOZ）是MYST家族的一种组蛋白乙酰转移酶，参与急性髓系白血病相关的染色体易位。MOZ作为AML1的转录辅激活因子，这对于确定造血至关重要。为了研究MOZ在正常造血中的作用，我们制造了MOZ缺失的小鼠。MOZ（-/-）小鼠在胚胎第15天（E15）左右死亡。在MOZ(-/-) E14.5胚胎中，造血干细胞、谱系承诺祖细胞和B谱系细胞严重减少。另一方面，观察到红系成熟阻滞和髓系种群升高。moz缺陷的胎儿肝细胞在移植后不能重建受体的造血功能。微阵列和流式细胞术分析显示，血小板生成素受体（c-Mpl）、HoxA9和c-Kit的表达下调。这些结果表明，MOZ是维持造血干细胞所必需的，并在红细胞和髓细胞的分化中发挥作用。MOZ（-/-）表型的某些方面与pu1缺陷小鼠相似。MOZ能够与PU.1相互作用并激活PU.1依赖的转录，从而表明PU.1与MOZ之间存在物理和功能上的联系。
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.