Migliaccio Anna Rita, Rana Rosa Alba, Vannucchi Alessandro M, Manzoli Francesco A
Department of Hematology, Oncology, and Molecular Medicine, Istituto Superiore Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Ann N Y Acad Sci. 2005 Jun;1044:142-58. doi: 10.1196/annals.1349.019.
GATA-1 exerts a concentration-dependent control on the differentiation of erythroid, megakaryocytic, mast, and eosinophilic cells. The concentration of GATA-1 is, in turn, regulated by specific sequences within the GATA-1 locus. On the basis of its levels of expression, the GATA-1 protein becomes associated with suitable partners forming transcription complexes that, by binding to lineage-specific enhancers, activate the expression of the corresponding target genes. Instrumental to our understanding of the role of GATA-1 in hemopoietic differentiation has been the generation of genetically engineered mutant mice and the discovery of naturally occurring mutations associated with either inherited or acquired human pathologies. We review our current understanding of the role of GATA-1 in normal and neoplastic hematopoiesis as emerging from these genetic approaches.
GATA-1对红系、巨核系、肥大细胞系和嗜酸性粒细胞系细胞的分化发挥浓度依赖性调控作用。反过来，GATA-1的浓度又受GATA-1基因座内特定序列的调控。根据其表达水平，GATA-1蛋白与合适的伙伴结合形成转录复合物，该复合物通过与谱系特异性增强子结合，激活相应靶基因的表达。基因工程突变小鼠的产生以及与遗传性或获得性人类疾病相关的自然发生突变的发现，对我们理解GATA-1在造血分化中的作用起到了重要作用。我们综述了从这些遗传学方法中所获得的关于GATA-1在正常和肿瘤性造血中作用的当前认识。
