Cloning and functional analysis of the mouse c-kit promoter.
Cloning and functional analysis of the mouse c-kit promoter.
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DOI：
10.1006/bbrc.1993.1301
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发表时间：
1993-03
影响因子：
3.1
通讯作者：
H. Yasuda;Stephen J. Galli;E. Geissler
中科院分区：
文献类型：
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作者：
H. Yasuda;Stephen J. Galli;E. Geissler
c-kit原癌基因编码酪氨酸激酶受体，在个体发育和成年生活中通过几个重要的和发育不同的细胞系表达。携带生殖系c-kit突变的小鼠在大多数这些谱系中表现出缺陷，表明c-kit功能对其正常发育是必要的。为了便于鉴定调节组织特异性c-kit表达的顺式作用元件，我们克隆并鉴定了一个在不同细胞类型中起作用的小鼠c-kit启动子。一个主要的c-kit转录起始位点（TIS）位于翻译起始密码子上游58 bp处，在小鼠肥大细胞和小鼠小脑的c-kit阳性细胞中被利用。5'侧区缺失对报告基因活性的影响确定了在小鼠和人c-kit阳性细胞系中起作用的三个短调控区域。该区域的核苷酸序列不包括CCAAT或TATA盒，但包含Sp1、Ap-2和几个短的富含ga的元件的一致结合位点，这些元件类似于ets结构域蛋白的结合位点。
The c-kit protooncogene encodes a tyrosine kinase receptor expressed during ontogeny and adult life by several important and developmentally distinct cell lineages. Mice carrying germ line c-kit mutations exhibit deficiencies in most of these lineages, demonstrating that c-kit function is necessary for their normal development. To facilitate the identification of cis-acting elements which regulate tissue-specific c-kit expression, we cloned and characterized a mouse c-kit promoter which is functional in different cell types. A major c-kit transcription initiation site (TIS), located 58 bp upstream from the translation initiation codon, is utilized in mouse mast cells and in c-kit-positive cells in the mouse cerebellum. The effects of deletions in the 5' flanking region on reporter gene activity identify three short regulatory regions which function in both mouse and human c-kit positive cell lines. The nucleotide sequence of this region does not include CCAAT or TATA boxes but contains consensus binding sites for Sp1, Ap-2 and several short GA-rich elements which resemble binding sites for the ETS-domain proteins.