C-KROX, A TRANSCRIPTIONAL REGULATOR OF TYPE-I COLLAGEN GENE-EXPRESSION, IS PREFERENTIALLY EXPRESSED IN SKIN
C-KROX, A TRANSCRIPTIONAL REGULATOR OF TYPE-I COLLAGEN GENE-EXPRESSION, IS PREFERENTIALLY EXPRESSED IN SKIN
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DOI：
10.1073/pnas.91.20.9372
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发表时间：
1994-09-27
影响因子：
11.1
通讯作者：
KARSENTY, G
中科院分区：
文献类型：
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作者：
GALERA, P;MUSSO, M;KARSENTY, G
我们克隆了一个小鼠cDNA，它是Krox基因家族的成员，编码一种我们命名为c-Krox的蛋白质。c-Krox蛋白含有三个Cys（2）His（2）型锌指。c-Krox特异性结合在小鼠α 1（I）胶原基因启动子元件中存在两次的富含鸟嘌呤的顺式作用元件。对c-Krox基因表达的研究表明，c-Krox在皮肤（I型胶原合成的两个主要位点之一）中显著富集，但在骨（另一个主要的I型胶原产生组织）中不存在，表明I型胶原基因表达在皮肤和骨中受到差异调节。在小鼠NM 3 T3成纤维细胞、表达c-Krox基因的细胞或不表达c-Krox的果蝇S2细胞中的DNA转染实验表明，c-Krox可以激活与α 1（I）胶原启动子中其结合位点的几个拷贝相连的报告基因的转录。因此，c-Krox只是Krox家族中第二个被鉴定出靶基因的成员。其mRNA表达的选择性空间模式及其转录激活能力表明，c-Krox可能是生理条件下和纤维化疾病如硬皮病中I型胶原皮肤特异性表达的重要调节剂。
We have cloned a mouse cDNA that is a member of the Krox gene family and encodes a protein we have named c-Krox. The c-Krox protein contains three zinc fingers of the Cys(2)His(2) type. c-Krox binds specifically to a guanine-rich cis-acting element present twice in the promoter element of the mouse alpha 1(I) collagen gene. Study of c-Krox gene expression shows that c-Krox is markedly enriched in skin, one of the two major sites of type I collagen synthesis, but is absent in bone, the other main type I collagen-producing tissue, indicating that type I collagen gene expression is differentially regulated in skin and bone. DNA transfection experiments in mouse NM 3T3 fibroblasts, cells that express the c-Krox gene, or in Drosophila S2 cells, which do not express c-Krox, reveal that c-Krox can activate transcription of a reporter gene linked to several copies of its binding site in the alpha 1(I) collagen promoter. Thus, c-Krox is only the second member of the Krox family for which a target gene has been identified. The selective spatial pattern of expression of its mRNA and its transcription activation ability suggest that c-Krox may be an important regulator of type I collagen skin specific expression in physiologic conditions and in fibrotic diseases such as scleroderma.