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人类细胞色素c1基因和泛醌结合蛋白基因5'侧翼区域中的常见蛋白质结合位点。

Common protein-binding sites in the 5'-flanking regions of human genes for cytochrome c1 and ubiquinone-binding protein.

作者信息

Suzuki H, Hosokawa Y, Toda H, Nishikimi M, Ozawa T

机构信息

Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.

出版信息

J Biol Chem. 1990 May 15;265(14):8159-63.

PMID:2159470
Abstract

The single nuclear gene encoding human ubiquinone-binding protein, a subunit of the cytochrome bc1 complex, was isolated previously (Suzuki, H., Hosokawa, Y., Toda, H., Nishikimi, M., and Ozawa, T. (1989) Biochem. Biophys. Res. Commun. 161, 371-378). The 5'-flanking region contains four putative CCAAT boxes, one putative NF-Y-binding site, and one sequence homologous to the AP-1 recognition site, but lacks typical TATA and GC boxes. Three common nucleotide sequences (5'-TATTCAGGT-3', 5'-ATCTGGCT-3', and 5'-TGGTGA(T/G)AG-3', designated Mt1, Mt3, and Mt4, respectively) were found in the 5'-flanking regions of the genes for human ubiquinone-binding protein and for human cytochrome c1, another subunit of the cytochrome bc1 complex. All three sequences are located in the 280-base pair BamHI-HindIII fragment of the ubiquinone-binding protein gene and in the 154-base pair SalI-PstI fragment of the cytochrome c1 gene. Interestingly, a computer-assisted homology search revealed that the SalI-PstI fragment of the cytochrome c1 gene is related to the long terminal repeat of an endogenous retrovirus. Sequences highly homologous to the three Mt-sequences were also found in the 5'-flanking regions of the genes for the beta subunit of human F0F1-ATPase and rat somatic cytochrome c. The Mt1 sequence (TATT-CAGGT) is similar to the GFII recognition site (RTCACGTG) found in the 5'-flanking regions of the yeast nuclear genes for three cytochrome bc1 complex subunits. Gel retardation assay demonstrated that protein factors in a whole HeLa cell extract bound to both of those fragments. At least three different specific binding sites were thought to exist in the fragments. Specific binding of the protein factors to the sites, possibly to the three Mt sequences, may play an important role in the coordinate regulation of the transcription of nuclear genes encoding subunits responsible for mitochondrial oxidative phosphorylation.

摘要

先前已分离出编码人泛醌结合蛋白(细胞色素bc1复合物的一个亚基)的单核基因(铃木,H.,细川,Y.,户田,H.,西木见,M.,及小泽,T.(1989年)《生物化学与生物物理学研究通讯》161,371 - 378)。其5'侧翼区包含四个假定的CCAAT框、一个假定的NF - Y结合位点以及一个与AP - 1识别位点同源的序列,但缺乏典型的TATA框和GC框。在人泛醌结合蛋白基因以及人细胞色素c1(细胞色素bc1复合物的另一个亚基)基因的5'侧翼区发现了三个常见核苷酸序列(分别为5'-TATTCAGGT-3'、5'-ATCTGGCT-3'和5'-TGGTGA(T/G)AG-3',命名为Mt1、Mt3和Mt4)。所有这三个序列都位于泛醌结合蛋白基因的280碱基对BamHI - HindIII片段以及细胞色素c1基因的154碱基对SalI - PstI片段中。有趣的是,计算机辅助同源性搜索显示细胞色素c1基因的SalI - PstI片段与一种内源性逆转录病毒的长末端重复序列相关。在人F0F1 - ATP酶β亚基基因和大鼠体细胞细胞色素c基因的5'侧翼区也发现了与这三个Mt序列高度同源的序列。Mt1序列(TATT - CAGGT)与在酵母核基因的5'侧翼区发现的三个细胞色素bc1复合物亚基的GFII识别位点(RTCACGTG)相似。凝胶阻滞试验表明,整个HeLa细胞提取物中的蛋白质因子与这两个片段都结合。据认为,这些片段中至少存在三个不同的特异性结合位点。蛋白质因子与这些位点(可能是与这三个Mt序列)的特异性结合可能在协调调控负责线粒体氧化磷酸化的亚基的核基因转录中起重要作用。

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