Dynamic regulation of Gata factor levels is more important than their identity
Dynamic regulation of Gata factor levels is more important than their identity
复制标题
DOI：
10.1182/blood-2006-11-060491
复制
发表时间：
2007-06-15
期刊：
影响因子：
20.3
通讯作者：
Philipsen, Sjaak
中科院分区：
文献类型：
--
作者：
Ferreira, Rita;Wai, Albert;Philipsen, Sjaak
三种加塔转录因子（Gatal、-2和-3）是造血所必需的。这些因素被认为发挥不同的作用，因为它们在功能上不能相互取代。例如，Gata 2信使RNA（mRNA）表达在Gata 1缺失的红细胞中高度升高，但这并不能挽救缺陷。在这里，我们测试Gata 2和-3转基因是否拯救Gata 1-null小鼠的红细胞缺陷，如果在适当的时空模式中表达。由β 3-珠蛋白调控元件驱动的Gatal、β 2和β 3转基因，将表达引导至分化的晚期阶段，未能挽救Gata 1无效突变体中的红细胞生成。相反，当由Gatal调控元件控制时，将表达引导至分化的早期阶段，Gata 1、Gata 2和Gata 3确实挽救了Gata 1-null表型。Gata 1-null祖细胞中内源性Gata 2 mRNA的急剧增加没有反映在Gata 2蛋白水平中，引起翻译调节。我们的数据表明，动态时空调节的加塔因子水平比他们的身份更重要，并提供了一个范式的发展控制机制，硬连线的顺式调控元件。
Three Gata transcription factors (Gatal, -2, and -3) are essential for hematopolesis. These factors are thought to play distinct roles because they do not functionally replace each other. For instance, Gata2 messenger RNA (mRNA) expression is highly elevated in Gata1-null erythrold cells, yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythrold defect of Gata1-null mice, if expressed in the appropriate spatiotemporal pattern. Gatal, -2, and -3 transgenes driven by j3-globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1-null mutants. In contrast, when controlled by Gatal regulatory elements, directing expression to the early stages of differentiation, Gata1, -2, and -3 do rescue the Gata1-null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1-null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatiotemporal regulation of Gata factor levels is more important than their identity and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements.