CLONING AND FUNCTIONAL-CHARACTERIZATION OF LCR-F1 - A BZIP TRANSCRIPTION FACTOR THAT ACTIVATES ERYTHROID-SPECIFIC, HUMAN GLOBIN GENE-EXPRESSION
CLONING AND FUNCTIONAL-CHARACTERIZATION OF LCR-F1 - A BZIP TRANSCRIPTION FACTOR THAT ACTIVATES ERYTHROID-SPECIFIC, HUMAN GLOBIN GENE-EXPRESSION
复制标题
DOI：
10.1093/nar/22.12.2383
复制
发表时间：
1994-06-25
影响因子：
14.9
通讯作者：
TOWNES, TM
中科院分区：
文献类型：
--
作者：
CATERINA, JJ;DONZE, D;TOWNES, TM
人β-珠蛋白基因位点控制区(LCR)的DNase I超敏部位2(HS 2)控制着位于下游50kb的β-珠蛋白基因的高水平表达。在培养细胞和转基因小鼠中的实验表明，这种强大的增强子活性需要在HS 2中复制AP1样位点。一个编码与这些位点结合的碱性亮氨酸拉链蛋白的cDNA克隆被分离出来，命名为LCR-F1。该蛋白是一个新的调控因子家族的成员，该家族包含一个63个氨基酸的‘cnD结构域’，与碱性区域重叠。该结构域在果蝇C帽N领(CnC)蛋白、NF-E2和LCR-F1中的同源性约为70%。在瞬时转染实验中，LCR-F1反式激活HS2/伽马珠蛋白报告基因170倍以上，特别是在红系细胞中。这些结果表明，LCR-F1可能是参与LCR介导的人类珠蛋白基因表达的关键因素。
DNase I hypersensitive site 2 (HS 2) of the human beta-globin Locus Control Region (LCR) directs high level expression of the beta-globin gene located 50 kilobases downstream. Experiments in cultured cells and in transgenic mice demonstrate that duplicated AP1-like sites in HS 2 are required for this powerful enhancer activity. A cDNA clone encoding a basic, leucine-zipper protein that binds to these sites was isolated and designated Locus Control Region-Factor 1 (LCR-F1). This protein is a member of a new family of regulatory factors that contain a 63 amino acid 'CNC domain' overlapping the basic region. This domain is approximately 70% identical in the Drosophila Cap N Collar (CNC) protein, NF-E2 and LCR-F1. LCR-F1 transactivates an HS 2/gamma-globin reporter gene over 170-fold in transient transfection experiments specifically in erythroid cells. These results suggest that LCR-F1 may be a critical factor involved in LCR-mediated, human globin gene expression.