Institute of Clinical Biochemistry, Hannover Medical School, Germany.
Mol Cell Endocrinol. 2011 Aug 6;342(1-2):8-19. doi: 10.1016/j.mce.2011.04.025. Epub 2011 Jun 6.
Kisspeptin, the product of the KiSS1 gene, has emerged as a key component of the mechanism by which the hypothalamus controls puberty and reproductive development. It does so by stimulating the secretion of gonadotropin releasing hormone (GnRH). Little is known about the transcriptional control of the KiSS1 gene. Here we show that a set of proteins postulated to be upstream components of a hypothalamic network involved in controlling female puberty regulates KiSS1 transcriptional activity. Using RACE-PCR we determined that transcription of KiSS1 mRNA is initiated at a single transcription start site (TSS) located 153-156bp upstream of the ATG translation initiation codon. Promoter assays performed using 293 MSR cells showed that the KiSS1 promoter is activated by TTF1 and CUX1-p200, and repressed by EAP1, YY1, and CUX1-p110. EAP1 and CUX-110 were also repressive in GT1-7 cells. All four TFs are recruited in vivo to the KiSS1 promoter and are expressed in kisspeptin neurons. These results suggest that expression of the KiSS1 gene is regulated by trans-activators and repressors involved in the system-wide control of mammalian puberty.
Kisspeptin，即 Kiss1 基因的产物，已成为下丘脑控制青春期和生殖发育的机制的关键组成部分。它通过刺激促性腺激素释放激素（GnRH）的分泌来实现这一点。关于 Kiss1 基因的转录控制知之甚少。在这里，我们展示了一组假定为参与控制女性青春期的下丘脑网络上游成分的蛋白质，它们调节 Kiss1 转录活性。使用 RACE-PCR，我们确定 Kiss1 mRNA 的转录起始于位于 ATG 翻译起始密码子上游 153-156bp 的单个转录起始位点（TSS）。使用 293 MSR 细胞进行的启动子测定表明，KiSS1 启动子被 TTF1 和 CUX1-p200 激活，并被 EAP1、YY1 和 CUX1-p110 抑制。EAP1 和 CUX-110 在 GT1-7 细胞中也具有抑制作用。这四个 TF 都在体内被募集到 KiSS1 启动子上，并在 kisspeptin 神经元中表达。这些结果表明，KiSS1 基因的表达受参与哺乳动物青春期系统控制的转录激活因子和转录抑制因子的调节。
