Critical role of the p400/mDomino chromatin‐remodeling ATPase in embryonic hematopoiesis
Critical role of the p400/mDomino chromatin‐remodeling ATPase in embryonic hematopoiesis
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DOI：
10.1111/j.1365-2443.2007.01080.x
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发表时间：
2007-05
期刊：
影响因子：
2.1
通讯作者：
Takeshi Ueda;Rie Watanabe‐Fukunaga;H. Ogawa;H. Fukuyama;Y. Higashi;S. Nagata;R. Fukunaga
中科院分区：
文献类型：
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作者：
Takeshi Ueda;Rie Watanabe‐Fukunaga;H. Ogawa;H. Fukuyama;Y. Higashi;S. Nagata;R. Fukunaga
SWI2/SNF2 家族 ATP 酶 p400/mDomino 是大型染色质重塑复合物的核心亚基，目前被认为在组蛋白变体交换（染色质结构改变的过程）中发挥独特的功能。在这里，我们通过生成定向删除 p400/mDomino N 端结构域（称为 mDomΔN/ΔN）的突变小鼠，研究了 p400/mDomino 在哺乳动物发育中的作用。 mDomΔN/ΔN小鼠在胚胎第11.5天（E11.5）死亡，并表现出贫血外观和神经管轻微畸形。 DNA微阵列和定量RT-PCR分析显示，所有胚胎珠蛋白基因和珠蛋白伴侣基因在E8.5的mDomΔN/ΔN胚胎和卵黄囊中表达较差，表明原始红细胞生成受损。造血集落测定表明，突变小鼠卵黄囊的造血活性显着受阻。我们还发现 mDomΔN/ΔN 卵黄囊中一组有限的 Hox 基因（包括 Hoxa7、Hoxa9 和 Hoxb9）的表达显着增强。这些结果表明，p400/mDomino 通过调节发育必需基因（例如 Hox 基因簇中的基因）的表达，在胚胎造血中发挥关键作用。
The SWI2/SNF2 family ATPase, p400/mDomino, is a core subunit of a large chromatin‐remodeling complex, and is currently suggested to play a unique function in histone variant exchange, a process by which chromatin structure is altered. Here, we investigated the role of p400/mDomino in mammalian development by generating mutant mice with a targeted deletion of the N‐terminal domain of p400/mDomino (referred to as mDomΔN/ΔN). The mDomΔN/ΔN mice died on embryonic day 11.5 (E11.5), and displayed an anemic appearance and slight deformity of the neural tube. DNA microarray and quantitative RT‐PCR analyses revealed that all of the embryonic globin genes and a globin chaperone gene were poorly expressed in the mDomΔN/ΔN embryo and yolk sac on E8.5, indicating that primitive erythropoiesis was impaired. A hematopoietic colony assay indicated that the hematopoietic activity of the yolk sac was significantly blocked in the mutant mice. We also found that the expression of a limited set of Hox genes, including Hoxa7, Hoxa9 and Hoxb9, was drastically enhanced in the mDomΔN/ΔN yolk sacs. These results suggest that p400/mDomino plays a critical role in embryonic hematopoiesis by regulating the expression of developmentally essential genes such as those in the Hox gene cluster.