Magis W, Martin D I
University of Washington School of Medicine, Seattle, USA.
Biochem Biophys Res Commun. 1995 Sep 25;214(3):927-33. doi: 10.1006/bbrc.1995.2375.
We have examined binding of the nuclear protein HMG-I to the human gamma-globin promoter. We find that HMG-I binds preferentially to the more 3' of a pair of GATA motifs in the gamma-globin promoter; this paired motif is bound by the erythroid factor GATA-1. A naturally occurring mutation (-175 T-C) in the area bound by HMG-I results in overexpression of gamma-globin in adult red blood cells (HPFH) and up-regulation of the gamma-globin promoter in in vitro expression assays; HMG-I does not bind to this mutant sequence. A survey of GATA motifs from other globin cis-elements demonstrates HMG-I binding to most of them. These findings implicate HMG-I in the HPFH phenotype; we speculate that it may participate in the formation of multiprotein complexes that regulate globin gene expression.
我们检测了核蛋白HMG-I与人γ-珠蛋白启动子的结合情况。我们发现HMG-I优先结合γ-珠蛋白启动子中一对GATA基序中更靠近3'端的那个；这对基序由红系因子GATA-1结合。HMG-I结合区域内一个天然存在的突变（-175 T-C）导致成人红细胞中γ-珠蛋白过度表达（遗传性胎儿血红蛋白持续存在症，HPFH），并且在体外表达试验中γ-珠蛋白启动子上调；HMG-I不与这个突变序列结合。对来自其他珠蛋白顺式元件的GATA基序进行的一项调查表明，HMG-I能与它们中的大多数结合。这些发现表明HMG-I与HPFH表型有关；我们推测它可能参与调节珠蛋白基因表达的多蛋白复合物的形成。
