Context-dependent function of "GATA switch" sites in vivo
Context-dependent function of "GATA switch" sites in vivo
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DOI：
10.1182/blood-2010-10-313031
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发表时间：
2011-05-05
期刊：
影响因子：
20.3
通讯作者：
Bresnick, Emery H.
中科院分区：
文献类型：
--
作者：
Snow, Jonathan W.;Trowbridge, Jennifer J.;Bresnick, Emery H.
发育的主要转录调节因子通常通过内源靶基因上分散的顺式元件发挥作用。虽然顺式元件在转染和转基因报告基因测定中被常规地研究，但确定它们在体内如何起作用是具有挑战性的。为了解决这个问题的基因座编码的关键造血转录因子Gata 2的上下文中，我们工程小鼠缺乏一个集群的加塔基序2.8 kb的Gata 2转录起始位点上游。我们证明了~ 2.8kb位点赋予造血干细胞和特异性造血祖细胞中的最大Gata 2表达。与我们先前的证明--在邻近的-1.8kb位点的回文加塔基序在终末分化的红系细胞中维持Gata 2阻遏相反，-2.8kb位点不需要启动或维持阻遏。这些分析揭示了2个含有加塔基序的区域在体内的定性不同的功能。（血。2011; 117918）：4769-4772）
Master transcriptional regulators of development often function through dispersed cis elements at endogenous target genes. While cis-elements are routinely studied in transfection and transgenic reporter assays, it is challenging to ascertain how they function in vivo. To address this problem in the context of the locus encoding the critical hematopoietic transcription factor Gata2, we engineered mice lacking a cluster of GATA motifs 2.8 kb upstream of the Gata2 transcriptional start site. We demonstrate that the -2.8 kb site confers maximal Gata2 expression in hematopoietic stem cells and specific hematopoietic progenitors. By contrast to our previous demonstration that a palindromic GATA motif at the neighboring -1.8 kb site maintains Gata2 repression in terminally differentiating erythroid cells, the -2.8 kb site was not required to initiate or maintain repression. These analyses reveal qualitatively distinct functions of 2 GATA motif-containing regions in vivo. (Blood. 2011; 117918): 4769-4772)