Hammer R E, Swift G H, Ornitz D M, Quaife C J, Palmiter R D, Brinster R L, MacDonald R J
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Mol Cell Biol. 1987 Aug;7(8):2956-67. doi: 10.1128/mcb.7.8.2956-2967.1987.
A total of 134 base pairs of the 5' flanking sequence of the elastase I gene is sufficient and necessary to direct expression of the passive human growth hormone gene (hGH) to the exocrine pancreas. We demonstrate that this elastase I regulatory region contains a transcriptional enhancer which directs acinar cell-specific expression in transgenic animals. The elastase I enhancer specifies correct expression of the linked hGH gene in an orientation- and position-independent manner and can activate a heterologous promoter. The enhancer also directs the appropriate temporal activation of the hGH gene in the developing pancreas. Transcription is initiated correctly for the elastase I or hGH promoter, and the transcripts are correctly processed regardless of the enhancer position within or outside the fusion gene. The elastase I enhancer generates coincident DNase I-hypersensitive sites in pancreatic chromatin when moved 3 kilobases upstream or within the first intron of the hGH gene and when associated with the hGH promoter.
弹性蛋白酶I基因5'侧翼序列的总共134个碱基对对于将人源化生长激素基因（hGH）定向表达至外分泌胰腺而言是充分且必要的。我们证明该弹性蛋白酶I调控区域包含一个转录增强子，其在转基因动物中指导腺泡细胞特异性表达。弹性蛋白酶I增强子以方向和位置独立的方式指定连接的hGH基因的正确表达，并且可以激活异源启动子。该增强子还指导hGH基因在发育中的胰腺中适时激活。对于弹性蛋白酶I或hGH启动子，转录起始正确，并且无论增强子在融合基因内或外的位置如何，转录本都能正确加工。当弹性蛋白酶I增强子向上游移动3千碱基或位于hGH基因的第一个内含子内并与hGH启动子相关联时，它会在胰腺染色质中产生一致的DNase I超敏位点。
