GATA1是一种高度保守的造血转录因子(TF),对于正常的红细胞生成和巨核细胞生成至关重要,编码全长,主要同种型和氨基(N)末端截短的同种型GATA1s。它在整个巨核细胞发育过程中始终表达,并独立地或与结合伴侣如FOG1(GATA1的朋友)相关地与其靶基因相互作用。虽然N端和锌指已经被证明是血小板特异性基因正常调节所必需的,鼠模型,细胞系研究,和人类病例报告表明,羧基末端激活域和锌指在精确控制巨核细胞生长中也起关键作用,扩散,和成熟。鼠模型已经显示,对GATA1的破坏增加了具有异常结构和受损的终末分化成血小板的未成熟巨核细胞的增殖。在人类中,种系GATA1突变导致可变的血细胞减少,包括血小板聚集异常和过度出血倾向的血小板减少症,而21三体(T21)患者的获得性GATA1s突变导致由巨核细胞-红系祖细胞(MEP)引起的短暂性骨髓异常生成(TAM)和唐氏综合征髓系白血病(ML-DS)。一起来看,GATA1在调节巨核细胞分化中起关键作用,成熟,和增殖能力。随着测序和蛋白质组学技术的发展,可能会揭示其他GATA1突变和导致人类巨核细胞和血小板疾病的调节机制。
GATA1 is a highly conserved hematopoietic transcription factor (TF), essential for normal erythropoiesis and megakaryopoiesis, that encodes a full-length, predominant isoform and an amino (N) terminus-truncated isoform GATA1s. It is consistently expressed throughout megakaryocyte development and interacts with its target genes either independently or in association with binding partners such as FOG1 (friend of GATA1). While the N-terminus and zinc finger have classically been demonstrated to be necessary for the normal regulation of platelet-specific genes, murine models, cell-line studies, and human case reports indicate that the carboxy-terminal activation domain and zinc finger also play key roles in precisely controlling megakaryocyte growth, proliferation, and maturation. Murine models have shown that disruptions to GATA1 increase the proliferation of immature megakaryocytes with abnormal architecture and impaired terminal differentiation into platelets. In humans, germline GATA1 mutations result in variable cytopenias, including macrothrombocytopenia with abnormal platelet aggregation and excessive bleeding tendencies, while acquired GATA1s mutations in individuals with trisomy 21 (T21) result in transient abnormal myelopoiesis (TAM) and myeloid leukemia of Down syndrome (ML-DS) arising from a megakaryocyte-erythroid progenitor (MEP). Taken together, GATA1 plays a key role in regulating megakaryocyte differentiation, maturation, and proliferative capacity. As sequencing and proteomic technologies expand, additional GATA1 mutations and regulatory mechanisms contributing to human diseases of megakaryocytes and platelets are likely to be revealed.