Li Yapeng, Qi Xiaopeng, Liu Bing, Huang Hua
Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; and.
J Immunol. 2015 May 1;194(9):4328-38. doi: 10.4049/jimmunol.1500018. Epub 2015 Mar 23.
Transcription factor GATA binding protein 2 (GATA2) plays critical roles in hematopoietic stem cell survival and proliferation, granulocyte-monocyte progenitor differentiation, and basophil and mast cell differentiation. However, precise roles of GATA2 in basophil and mast cell differentiation and maintenance have not been delineated. We have identified GATA2 as an essential transcription factor in differentiation of newly identified common basophil and mast cell progenitors into basophils and mast cells. We observed Gata2 haploinsufficiency for mast cell differentiation, but not for basophil differentiation. We examined the precise role of GATA2 in maintaining the expression of a wide range of genes that are important for performing basophil or mast cell functions. The effects of GATA2 on gene expression were broadly based. We demonstrated that GATA2 was required for maintaining Fcer1a mRNA and FcεRIα protein expression on both basophils and mast cells, as well as for maintaining Kit mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for Il4 mRNA expression in basophils and Il13 mRNA expression in mast cells. We demonstrate a STAT5-GATA2 connection, showing that the STAT5 transcription factor directly bound to the promoter and an intronic region of the Gata2 gene. Overexpression of the Gata2 gene was sufficient to direct basophil and mast cell differentiation in the absence of the Stat5 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance.
转录因子GATA结合蛋白2（GATA2）在造血干细胞的存活和增殖、粒细胞-单核细胞祖细胞分化以及嗜碱性粒细胞和肥大细胞分化中发挥着关键作用。然而，GATA2在嗜碱性粒细胞和肥大细胞分化及维持中的具体作用尚未明确。我们已确定GATA2是新发现的共同嗜碱性粒细胞和肥大细胞祖细胞分化为嗜碱性粒细胞和肥大细胞过程中的一种必需转录因子。我们观察到Gata2单倍剂量不足会影响肥大细胞的分化，但不影响嗜碱性粒细胞的分化。我们研究了GATA2在维持一系列对嗜碱性粒细胞或肥大细胞功能至关重要的基因表达中的具体作用。GATA2对基因表达的影响是广泛的。我们证明，GATA2是维持嗜碱性粒细胞和肥大细胞上Fcer1a mRNA和FcεRIα蛋白表达以及维持肥大细胞上Kit mRNA和c-Kit蛋白表达所必需的。GATA2是组胺合成所必需的，对嗜碱性粒细胞中Il4 mRNA表达和肥大细胞中Il13 mRNA表达也至关重要。我们证明了STAT5与GATA2之间的联系，表明STAT5转录因子直接结合到Gata2基因的启动子和一个内含子区域。在没有Stat5基因的情况下，Gata2基因的过表达足以指导嗜碱性粒细胞和肥大细胞的分化。我们的研究表明，STAT5-GATA2途径对嗜碱性粒细胞和肥大细胞的分化及维持至关重要。
