An albumin enhancer located 10 kb upstream functions along with its promoter to direct efficient, liver-specific expression in transgenic mice.
Transgenic mice were used to locate the cis-acting DNA elements that are important for efficient, tissue-specific expression of the mouse albumin gene in the adult. Chimeric genes with up to 12 kb of mouse albumin 5'-flanking region fused to a human growth hormone (hGH) reporter gene were tested. Remarkably, a region located 8.5-10.4 kb upstream of the albumin promoter was essential for high-level expression in adult liver and the region in between -8.5 and -0.3 kb was dispensable. The far-upstream region behaved like an enhancer in that its position and orientation relative to the albumin promoter were not critical; however, it did not function well with a heterologous promoter. Two of four DNase hypersensitive sites found in the 5'-flanking region of the albumin gene map to the far-upstream and promoter regions; the others may reflect regions involved in developmental or environmental control of this gene.
Pinkert
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CA
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, 19104.
Ornitz
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DM
Brinster
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RL
Palmiter
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RD
D000818:Animals; D001482:Base Composition; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D005796:Genes; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012709:Serum Albumin / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D012709:Serum Albumin; D013006:Growth Hormone