Woodson K G, Crawford P A, Sadovsky Y, Milbrandt J
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mol Endocrinol. 1997 Feb;11(2):117-26. doi: 10.1210/mend.11.2.9881.
Steroidogenic factor 1 (SF-1) is a transcription factor shown to be critical for regulation of adrenal and gonadal development and function. To dissect the mechanisms that direct expression of this regulator, we have studied the promoter of the SF-1 gene and have identified cis-acting elements that recognize a basic-helix-loop-helix transcription factor; the CAAT binding factor; and Sp1. We demonstrate in Y1 adrenocortical cells that a 90-bp proximal promoter fragment is sufficient to direct steroidogenic-specific expression and that all three elements are required for activity of the SF-1 promoter. Functional analysis of the binding sites on a heterologous TATA box-containing promoter demonstrates that the CAAT box and Sp1 site are not essential for promoter activity when a TATA box is present, whereas the E box is absolutely required for gene expression and is most likely the steroidogenic cell-specific element. We also demonstrate that SF-1 itself does not significantly affect the transcription of its own gene, and thus conclude that the E box, CAAT box, and Sp1 site of the proximal promoter direct expression of the SF-1 gene.
类固醇生成因子1（SF-1）是一种转录因子，已证明其对肾上腺和性腺的发育及功能调节至关重要。为剖析指导该调节因子表达的机制，我们研究了SF-1基因的启动子，并鉴定出了识别一种碱性螺旋-环-螺旋转录因子、CAAT结合因子和Sp1的顺式作用元件。我们在Y1肾上腺皮质细胞中证明，一个90bp的近端启动子片段足以指导类固醇生成特异性表达，且这三个元件都是SF-1启动子活性所必需的。对含异源TATA框启动子上结合位点的功能分析表明，当存在TATA框时，CAAT框和Sp1位点对启动子活性并非必需，而E框对于基因表达是绝对必需的，并且很可能是类固醇生成细胞特异性元件。我们还证明，SF-1本身不会显著影响其自身基因的转录，因此得出结论，近端启动子的E框、CAAT框和Sp1位点指导SF-1基因的表达。
