Nomura M, Bärtsch S, Nawata H, Omura T, Morohashi K
Department of Molecular Biology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
J Biol Chem. 1995 Mar 31;270(13):7453-61. doi: 10.1074/jbc.270.13.7453.
Ad4BP, also known as SF-1, is a cell type-specific transcription factor regulating all the steroidogenic P-450 genes. Recently, the targeted disruption of the mouse ftz-f1 gene encoding Ad4BP/SF-1 has established its essential function in both adrenal and gonadal development and sexual differentiation. As an initial step toward understanding its role in the cascade of gene activations necessary for the differentiation of the steroidogenic tissues and the sex differentiation of the gonads, we isolated and characterized the rat ad4bp gene. A sequence analysis of the ad4bp gene revealed that another nuclear factor ELP was also transcribed from the same gene by alternative promoter usage and splicing. The promoter of the ad4bp gene showed activities in the steroidogenic cells such as Y-1 adrenocortical cells and I-10 testicular Leydig cells when examined by transient transfection assays. Using deletion analysis and site-directed mutagenesis, we identified a cis-element at the position from -82 bp to -77 bp in the 5'-upstream region. The cis-element was identical to the consensus E box element, which is the binding site for the basic-helix-loop-helix proteins. Gel mobility shift analyses revealed the amount of a binding factor to this E box in the nuclear extract prepared from the rat testes attained a maximal level 1 week after birth and then decreased dramatically thereafter, and only trace amounts were detected in adult rats. In contrast, the binding factor in the ovaries attained a maximal level just after birth and kept its level thereafter. These dimorphic expressions of the binding factor to the E box correlated well with those of Ad4BP, and thus suggested that the expression of Ad4BP, and thus suggested that the expression of Ad4BP is transcriptionally regulated through this E box element.
Ad4BP,也被称为SF-1,是一种细胞类型特异性转录因子,可调控所有类固醇生成的P-450基因。最近,对编码Ad4BP/SF-1的小鼠ftz-f1基因进行靶向破坏,已证实其在肾上腺和性腺发育及性别分化中具有重要功能。作为理解其在类固醇生成组织分化和性腺性别分化所需基因激活级联反应中作用的第一步,我们分离并鉴定了大鼠ad4bp基因。对ad4bp基因的序列分析表明,另一种核因子ELP也通过交替使用启动子和剪接从同一基因转录而来。通过瞬时转染实验检测发现,ad4bp基因的启动子在类固醇生成细胞如Y-1肾上腺皮质细胞和I-10睾丸间质细胞中具有活性。利用缺失分析和定点诱变,我们在5'上游区域-82 bp至-77 bp的位置鉴定出一个顺式元件。该顺式元件与共有E盒元件相同,后者是碱性螺旋-环-螺旋蛋白的结合位点。凝胶迁移率变动分析显示,从大鼠睾丸制备的核提取物中与该E盒结合的因子量在出生后1周达到最高水平,此后急剧下降,在成年大鼠中仅检测到微量。相反,卵巢中的结合因子在出生后即刻达到最高水平,并在此后保持该水平。与E盒结合的因子的这些二态性表达与Ad4BP的表达密切相关,因此表明Ad4BP的表达是通过该E盒元件进行转录调控的。