Globin gene switching - In vivo protein-DNA interactions of the human beta-globin locus in erythroid cells expressing the fetal or the adult globin gene program
Globin gene switching - In vivo protein-DNA interactions of the human beta-globin locus in erythroid cells expressing the fetal or the adult globin gene program
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DOI：
10.1074/jbc.271.24.14082
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发表时间：
1996-06-14
影响因子：
4.8
通讯作者：
Kan, YW
中科院分区：
文献类型：
--
作者：
Ikuta, T;Papayannopoulou, T;Kan, YW
为了表征对人类β-珠蛋白基因座的发育控制重要的蛋白质-DNA相互作用，我们通过体内硫酸二甲酯足迹红细胞表达胎儿或成人珠蛋白发育程序进行分析，在β-珠蛋白基因座的基因座控制区（LCR）中，NF-EB（或AP-1）和GATA-1基序上的体内足迹仍然存在 无论是胎儿还是成人珠蛋白基因的表达都是相同的。相反，表达胎儿或成体珠蛋白程序的细胞之间 GT (CACCC) 基序的体内足迹不同。在启动子区域，活跃转录的基因在典型元件（例如 CACCC 和 CCAAT 基序）上表现出广泛且一致的足迹。成体珠蛋白表达细胞在 3' 调节中比胎儿珠蛋白表达细胞显示出更广泛的足迹。 (A) γ-和β-珠蛋白基因的序列，表明这些3'元件在β-珠蛋白基因表达中的作用。我们的结果表明，作为珠蛋白基因发育控制基础的大部分蛋白质-DNA相互作用发生在γ-和β-珠蛋白基因启动子中，并且β-珠蛋白位点LCR的GT基序可能在发育中发挥作用。 人类β-珠蛋白基因表达的调节，可能是通过增加LCR全复合物与胎儿或成人珠蛋白基因相互作用的可能性。
To characterize the protein-DNA interactions important for the developmental control of the human beta-globin locus, we analyzed by in vivo dimethyl sulfate footprinting erythroid cells expressing either the fetal or the adult globin developmental program, In the locus control region (LCR) of the beta-globin locus, in vivo footprints on NF-EB (or AP-1) and GATA-1 motifs remained the same regardless of whether the fetal or the adult globin genes are expressed. In contrast, in vivo footprints on GT (CACCC) motifs differed between the cells expressing the fetal or the adult globin program, In promoter regions, the actively transcribed genes demonstrated extensive and consistent footprints over the ca nonical elements, such as CACCC and CCAAT motifs, The adult globin expressing cells displayed more extensive footprints than the fetal globin expressing cells in the 3' regulatory sequences of both the (A) gamma- and the beta-globin genes, suggesting a role of these 3' elements in beta-globin gene expression, Our results suggest that the bulk of protein-DNA interactions that underlies the developmental control of globin genes takes place in the gamma- and beta-globin gene promoters, and that GT motifs of the beta-globin locus LCR may play a role in the developmental regulation of human beta-globin gene expression, perhaps by increasing the probability of interaction of the LCR holocomplex with the fetal or the adult globin gene.