GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation
GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation
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DOI：
10.1111/gtc.12086
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发表时间：
2013-11-01
期刊：
影响因子：
2.1
通讯作者：
Yamamoto, Masayuki
中科院分区：
文献类型：
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作者：
Suzuki, Mikiko;Kobayashi-Osaki, Maki;Yamamoto, Masayuki
转录因子GATA 2在造血干细胞和祖细胞中高度表达，而其表达在祖细胞的红系定型后下降。相反，GATA 1表达的开始与红系定型一致，并随着红系分化沿着增加。我们将加塔因子表达的这种动态转换称为“加塔因子切换”。在这里，我们研究了加塔因子转换对红系分化的贡献。在同时表达Gata 2-GFP报告基因的Gata 1敲除胚胎中，在分化受损的积累的未成熟造血细胞中检测到GFP报告基因的高水平表达，表明GATA 1在体内抑制造血祖细胞中的Gata 2基因表达。我们已经进行了染色质免疫沉淀（ChIP）的GATA 2和GATA 1的微阵列分析，结果表明，GATA 1结合位点广泛重叠的GATA 1表达前由GATA 2预先占据的网站。重要的是，具有被GATA 1和GATA 2两者结合的加塔盒的红系基因倾向于在未成熟的红系细胞中表达，而那些具有GATA 1高度结合而GATA 2仅弱结合的加塔盒的红系基因对于成熟的红系细胞功能是重要的。因此，我们的研究结果支持的论点，即先前的GATA 2的结合有助于随后的GATA 1的结合，从而确保顺利表达的瞬时相基因。
Transcription factor GATA2 is highly expressed in hematopoietic stem cells and progenitors, whereas its expression declines after erythroid commitment of progenitors. In contrast, the start of GATA1 expression coincides with the erythroid commitment and increases along with the erythroid differentiation. We refer this dynamic transition of GATA factor expression to as the GATA factor switching'. Here, we examined contribution of the GATA factor switching to the erythroid differentiation. In Gata1-knockdown embryos that concomitantly express Gata2-GFP reporter, high-level expression of GFP reporter was detected in accumulated immature hematopoietic cells with impaired differentiation, demonstrating that GATA1 represses Gata2 gene expression in hematopoietic progenitors in vivo. We have conducted chromatin immunoprecipitation (ChIP) on microarray analyses of GATA2 and GATA1, and results indicate that the GATA1-binding sites widely overlap with the sites pre-occupied by GATA2 before the GATA1 expression. Importantly, erythroid genes harboring GATA boxes bound by both GATA1 and GATA2 tend to be expressed in immature erythroid cells, whereas those harboring GATA boxes to which GATA1 binds highly but GATA2 binds only weakly are important for the mature erythroid cell function. Our results thus support the contention that preceding binding of GATA2 helps the following binding of GATA1 and thereby secures smooth expression of the transient-phase genes.