Chavrier P, Janssen-Timmen U, Mattéi M G, Zerial M, Bravo R, Charnay P
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Mol Cell Biol. 1989 Feb;9(2):787-97. doi: 10.1128/mcb.9.2.787-797.1989.
We have analyzed the structure and the regulation of Krox-20, a mouse zinc finger-encoding gene which is transiently activated following serum stimulation of quiescent fibroblast cells in culture. The gene is localized on chromosome 10, band B5, in the mouse, and the homologous human gene also maps to chromosome 10 (region q21.1 to q22.1). Alternative splicing of the 5'-most intron of the Krox-20 gene gives rise to mRNAs encoding putative zinc finger proteins with different N termini. The first exon contains a sequence element with strong similarity to the c-fos proto-oncogene serum response element (SRE). This element can functionally substitute for the c-fos SRE, and it binds the same nuclear protein. It is probably responsible for the serum induction of Krox-20, possibly in combination with a weaker SRE located in the 5'-flanking region of the gene. Our findings suggest that c-fos, Krox-20, and a number of immediate-early serum response genes are coregulated and that the SRE and its cognate protein are essential components of this regulatory pathway.
我们分析了Krox-20的结构及其调控机制。Krox-20是一个小鼠锌指编码基因,在培养的静止成纤维细胞受到血清刺激后会被短暂激活。该基因定位于小鼠的10号染色体B5带,其同源的人类基因也定位于10号染色体(q21.1至q22.1区域)。Krox-20基因5'端最内侧内含子的可变剪接产生了编码具有不同N端的假定锌指蛋白的mRNA。第一个外显子包含一个与c-fos原癌基因血清反应元件(SRE)有高度相似性的序列元件。该元件在功能上可替代c-fos SRE,并能结合相同的核蛋白。它可能负责血清对Krox-20的诱导,可能与位于该基因5'侧翼区域的一个较弱的SRE共同作用。我们的研究结果表明,c-fos、Krox-20和一些早期血清反应基因是共同调控的,并且SRE及其同源蛋白是该调控途径的重要组成部分。