The rat elastase I regulatory element is an enhancer that directs correct cell specificity and developmental onset of expression in transgenic mice.
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.
Hammer
R E
RE
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Swift
G H
GH
Ornitz
D M
DM
Quaife
C J
CJ
Palmiter
R D
RD
Brinster
R L
RL
MacDonald
R J
RJ
D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005796:Genes; D005809:Genes, Regulator; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D006824:Hybridization, Genetic; D051379:Mice; D008815:Mice, Inbred Strains; D009693:Nucleic Acid Hybridization; D010196:Pancreatic Elastase / Q000235:genetics*; D014158:Transcription, Genetic
D013006:Growth Hormone; D010196:Pancreatic Elastase