WASH蛋白可通过招募NURF复合物调控造血干细胞分化

在这篇题为“WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc–dependent manner”的论文中，研究人员通过将WASHflox/flox小鼠与骨髓系统特异Cre即Mx1-Cre小鼠交配，得到了能够通过注射聚肌胞苷酸（polyI:C）诱导骨髓系统中WASH基因敲除的小鼠并发现，当WASH基因在小鼠造血系统中被特异性敲除时，小鼠出现严重贫血，呈现明显的外周血液细胞数目降低和骨髓系统造血前体细胞数目减少的现象。

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(VEGFR1)

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体内长期重建实验表明，WASH基因缺失的长期造血干细胞的分化能力受到了抑制。通过基因表达谱芯片的分析发现，WASH基因缺失后细胞内c-Myc的表达出现了明显的下降。而c-Myc是调控造血干细胞分化的重要转录因子，c-Myc基因缺失的小鼠表现出与WASH基因敲除的小鼠同样的特征。研究发现，WASH蛋白能够与c-Myc基因的启动子区域结合从而直接调控c-Myc基因的转录。进一步研究发现，WASH蛋白通过招募NURF复合物，附着在c-Myc基因的启动子区域，启动了对c-Myc基因转录的正向调控。因此，WASH蛋白在调控造血干细胞分化中具有重要的作用。（