Functional interaction of GATA1 with erythroid Kruppel-like factor and SP1 at defined erythroid promoters
Functional interaction of GATA1 with erythroid Kruppel-like factor and SP1 at defined erythroid promoters
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DOI：
10.1182/blood.v87.5.1793.bloodjournal8751793
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发表时间：
1996-03-01
期刊：
影响因子：
20.3
通讯作者：
Wojchowski, DM
中科院分区：
文献类型：
--
作者：
Gregory, RC;Taxman, DJ;Wojchowski, DM
GATA和CACC元件通常在多种红系基因的调控区域内共分布。利用果蝇S2细胞，研究了GATA1、Sp1和红细胞kruppel样因子（EKLF）在模型红细胞启动子中这些元件上的作用。对于研究的每一个启动子（红系丙酮酸激酶、糖蛋白B和小鼠β（主要）球蛋白衍生构建体GCT） Sp1和EKLF，尽管CACC元件序列、取向和定位不同，但它们都激活了转录。然而，GATA1在丙酮酸激酶启动子上与Spl明显协同作用；在β（主要）珠蛋白衍生的GCT启动子上有EKLF；并且在糖蛋白B启动子处含有Spl或EKLF。因此，GATA1可能在功能上与这些kruppel样因子相互作用，这取决于启动子上下文；在GCT启动子处，GATA1和EKLF的转录激活比可归因于加性效应的水平高10倍以上。杆状病毒表达的EKLF与GATA1的特异性结合支持了这些激活剂之间直接相互作用的可能性。该报告强调Sp1和EKLF在红细胞基因激活中可能存在不同的作用。并支持EKLF和GATA1作为共同调控因子的直接协同机制。(C) 1996年由美国血液病学会出版。
GATA and CACC elements commonly are codistributed within the regulatory domains of a variety of erythroid genes. Using Drosophila S2 cells, the actions of GATA1, Sp1, and erythroid Kruppel-like factor (EKLF) at these elements within model erythroid promoters have been assessed. For each promoter studied (erythroid pyruvate kinase, glycophorin B, and a murine beta(maj) globin-derived construct, GCT) Sp1 and EKLF each activated transcription despite differences in CACC element sequence, orientation, and positioning. However, GATA1 acted in apparent cooperativity with Spl at the pyruvate kinase promoter; with EKLF at the beta(maj) globin-derived GCT promoter; and with either Spl or EKLF at the glycophorin B promoter. Thus, GATA1 may functionally interact with each of these Kruppel-like factors depending on promoter context; and at the GCT promoter, transcriptional activation by GATA1 and EKLF was greater than or equal to 10-fold higher than levels attributable to additive effects. The possibility that interactions between these activators may be direct was supported by the specific binding of baculoviral-expressed EKLF to GATA1. This report underlines the likelihood that discrete roles exist for Sp1 and EKLF in erythroid gene activation. and supports a mechanism of direct cooperativity for EKLF and GATA1 as coregulators. (C) 1996 by The American Society of Hematology.