Localization of a liver-specific enhancer in the apolipoprotein E/C-I/C-II gene locus.
The sequences necessary for liver-specific expression of the apolipoprotein (apo) E gene have been shown to reside 3' to the gene, within the apoE/C-I/C-II gene cluster, but have not been precisely characterized. Utilizing a transient transfection reporter gene assay based on the apoC-II promoter, we have localized a liver-specific enhancer to its approximate limit dimension of 154 base pairs. This enhancer directed liver-specific expression of an apoE gene construction in transgenic mice. A DNaseI protection assay revealed two footprints over an inverted repeat of a known transcriptionally active motif, TGACCT. DNaseI-sensitive sites were present in three of six repeats of a motif (consensus GCAAACA) which has been postulated to represent the recognition sequence of a hepatic transcriptional activity, HNF-5. This region of DNA may function as a liver-specific enhancer for the entire apoE/C-I/C-II gene cluster.
Shachter
N S
NS
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021-6399.
Zhu
Y
Y
Walsh
A
A
Breslow
J L
JL
Smith
J D
JD
D000818:Animals; D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D053302:Apolipoprotein C-I; D053304:Apolipoprotein C-II; D001056:Apolipoproteins C; D001057:Apolipoproteins E; D003850:Deoxyribonuclease I