The human alpha 2 integrin gene promoter. Identification of positive and negative regulatory elements important for cell-type and developmentally restricted gene expression.
The human alpha 2 integrin gene promoter. Identification of positive and negative regulatory elements important for cell-type and developmentally restricted gene expression.
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人类α2整合素基因启动子。
DOI：
10.1016/s0021-9258(17)42373-8
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
A. Gafford
中科院分区：
文献类型：
--
作者：
M. Zutter;Samuel A. Santoro;A. Painter;Ying L. Tsung;A. Gafford
α 2 β 1作为胶原蛋白受体或胶原蛋白/层粘连蛋白受体，这取决于细胞类型。整合素的表达在正常细胞分化过程中受到调节，并在癌变过程中发生改变。我们以前已经证明，在巨核细胞分化过程中，α 2 β 1整合素的表达增加是由于α 2整合素基因的转录激活而导致α 2 mRNA增加的结果，而乳腺癌中整合素的表达减少是由于α 2 mRNA的稳态水平降低。我们现在报告α 2整合素基因的5 '侧翼区的鉴定和表征。α 2 mRNA的5 '非翻译区向翻译起始位点5'延伸129个碱基对。启动子区缺乏TATA和CAAT盒，但含有一个缩写的起始序列和6个Sp1结合位点。还存在AP-1和AP-2复合物的共有结合位点、一个加塔盒、一个Pu.1盒和两个具有结合雌激素受体潜力的回文基序。5’-侧翼区的961-碱基对片段指导T47-D上皮细胞和多能造血K562细胞在巨核细胞分化时报告基因的细胞类型特异性和分化特异性表达。
The alpha 2 beta 1 serves as a collagen receptor or a collagen/laminin receptor, depending upon cell type. Expression of the integrin is regulated during normal cellular differentiation and is altered during carcinogenesis. We have previously demonstrated that increased expression of the alpha 2 beta 1 integrin during megakaryocytic differentiation is a consequence of increased alpha 2 mRNA due to transcriptional activation of the alpha 2 integrin gene and that the decreased expression of the integrin in breast adenocarcinoma is due to decreased steady-state levels of alpha 2 mRNA. We now report the identification and characterization of the 5'-flanking region of the alpha 2 integrin gene. The 5'-untranslated region of the alpha 2 mRNA extends 129 base pairs 5' to the site of translation initiation. The promoter region lacks TATA and CAAT boxes but contains an abbreviated initiator sequence and six Sp1 binding sites. Consensus binding sites for AP-1 and AP-2 complexes, a GATA box, a Pu.1 box, and two palindromic motifs with potential to bind the estrogen receptor are also present. A 961-base pair fragment of the 5'-flanking region directs both cell type- and differentiation-specific expression of a reporter gene in T47-D epithelial cells and in pluripotent hematopoietic K562 cells upon megakaryocytic differentiation.