Drouin J, Nemer M, Charron J, Gagner J P, Jeannotte L, Sun Y L, Therrien M, Tremblay Y
Institut de recherches cliniques de Montréal, Québec, Canada.
Genome. 1989;31(2):510-9. doi: 10.1139/g89-099.
The gene encoding pro-opiomelanocortin (POMC) is specifically expressed in two different cell types of the pituitary gland. We have defined the regulatory DNA sequences of the POMC gene that are responsible for this cell-specific expression. In addition, we have defined a regulatory element, located in the proximal region of the POMC promoter, that confers glucocorticoid repression in the anterior pituitary. Using DNA-mediated gene transfer into transgenic mice and tissue culture cells, the POMC regulatory sequences required for cell-specific expression and glucocorticoid repression were localized within a 543-bp fragment in the 5'-flanking region of the gene. Multiple regulatory elements that bind nuclear proteins are present within this region. In particular, a sequence that binds the glucocorticoid receptor and behaves as a "negative glucocorticoid response element" (nGRE) also binds nuclear proteins of the COUP (chicken ovalbumin upstream promoter) family of transcription factors. Thus, glucocorticoid repression of POMC transcription may result from the mutually exclusive binding of the glucocorticoid receptor and the COUP transcription factor to the POMC nGRE.
编码阿黑皮素原（POMC）的基因在垂体的两种不同细胞类型中特异性表达。我们已经确定了负责这种细胞特异性表达的POMC基因的调控DNA序列。此外，我们还确定了一个位于POMC启动子近端区域的调控元件，该元件在前垂体中赋予糖皮质激素抑制作用。通过将DNA介导的基因转移到转基因小鼠和组织培养细胞中，细胞特异性表达和糖皮质激素抑制所需的POMC调控序列定位在该基因5'侧翼区域的一个543 bp片段内。该区域存在多个与核蛋白结合的调控元件。特别是，一个与糖皮质激素受体结合并表现为“负糖皮质激素反应元件”（nGRE）的序列也与COUP（鸡卵清蛋白上游启动子）转录因子家族的核蛋白结合。因此，POMC转录的糖皮质激素抑制可能是由于糖皮质激素受体和COUP转录因子与POMC nGRE相互排斥结合所致。
