GATA1 mutations in red cell disorders
GATA1 mutations in red cell disorders
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DOI：
10.1002/iub.2177
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发表时间：
2019-10-25
期刊：
影响因子：
4.6
通讯作者：
Crispino, John D.
中科院分区：
文献类型：
--
作者：
Ling, Te;Crispino, John D.
GATA 1是红系细胞基因表达和成熟的重要调节因子。在其不存在的情况下，红系祖细胞在分化中被阻止并经历凋亡。通过动物模型，包括基因敲除以及表达水平降低的动物模型，已经对GATA 1的功能有了很多了解。然而，更大的见解来自于发现一些罕见的红细胞疾病，包括Diamond-Blackfan贫血，与GATA 1突变有关。这些突变影响氨基末端锌指（N-ZF）和蛋白质的氨基末端，并且在这两种情况下可以改变DNA结合活性，这主要由第三个功能结构域，羧基末端锌指（C-ZF）赋予。在这里，我们讨论的作用，GATA 1在红细胞生成的突变，在人类红细胞疾病患者中发现的重点。
GATA1 is an essential regulator of erythroid cell gene expression and maturation. In its absence, erythroid progenitors are arrested in differentiation and undergo apoptosis. Much has been learned about GATA1 function through animal models, which include genetic knockouts as well as ones with decreased levels of expression. However, even greater insights have come from the finding that a number of rare red cell disorders, including Diamond-Blackfan anemia, are associated with GATA1 mutations. These mutations affect the amino-terminal zinc finger (N-ZF) and the amino-terminus of the protein, and in both cases can alter the DNA-binding activity, which is primarily conferred by the third functional domain, the carboxyl-terminal zinc finger (C-ZF). Here we discuss the role of GATA1 in erythropoiesis with an emphasis on the mutations found in human patients with red cell disorders.