基因组的结构和转录调控人类生长激素促分泌素受体。
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拉希Petersenn年代,AC, Penshorn M,胆汁酸的福,舒尔特嗯
基因组的结构和转录调控人类生长激素促分泌素受体。
内分泌学。2001年6月,142 (6):2649 - 59。
- PubMed ID
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11356716 (在PubMed]
- 文摘
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合成GH促分泌素刺激GH通过绑定到最近克隆特定GH促分泌素受体(GHS-R)。这个受体的内源性配体可能是一个新的内分泌控制GH分泌途径。两个不同的受体变异,类型1 a和1 b,描述了不同的3 '末端氨基酸。我们调查了基因组结构和人类GHS-R的转录调控。18 kb基因组克隆包括序列编码两个GHS-R变体是孤立的。测序表明这两个变种起源于特定的单个基因的RNA加工跨度大约4.1 kb。定义的转录开始网站5 '逆PCR分析在-227位置。rt - pcr分析表明微分转录起始和处理。1型由两个外显子编码;2152个基点intronic序列被拼接在796/797的位置相对于翻译网站开始。 Type 1b is encoded by a single exon. A putative polyadenylation signal consensus motif was identified at position +4118; 2.7 kb of the 5'-flanking region were sequenced, and putative transcription factor binding sites were identified. Transcriptional regulation was investigated by transient transfections using promoter fragments ranging in size from 168-1745 bp; 1745 bp of the GHS-R promoter directed significant levels of luciferase expression in GH(4) rat pituitary cells, whereas no activity was detected in monkey kidney COS-7 cells, human endometrium Skut-1B cells, mouse hypothalamic LHRH neuronal GT1-7 cells, or mouse corticotroph pituitary AtT20 cells. A minimal 309-bp promoter allowed pituitary-specific expression. Its activity in COS-7 cells was enhanced by cotransfection of the pituitary-specific transcription factor Pit-1. We did not find any regulation of the GHS-R promoter by forskolin, somatostatin, insulin-like growth factor I, or 12-O-tetraphorbol 12-myristate 13-acetate. Thyroid hormone and estrogen lead to a significant stimulation; glucocorticoids lead to a significant inhibition. Further mapping suggests a thyroid hormone-responsive element, an estrogen-responsive element, and a glucocorticoid-responsive element located between -309 and the translation start codon. These studies demonstrate the nature of the human GHS-R gene and identify its 5'-flanking region. Furthermore, pituitary-specific activity of the promoter and regulation by various hormones are demonstrated.