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 apolipopr otein (apo) E gene have been shown to reside 3' to the gene, within th e apoE/C-I/C-II gene cluster, but have not been precisely characterize d. 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 m ice. A DNaseI protection assay revealed two footprints over an inverte d repeat of a known transcriptionally active motif, TGACCT DNaseI-sens itive sites were present in three of six repeats of a motif (consensus GCAAACA) which has been postulated to represent the recognition seque nce of a hepatic transcriptional activity, HNF-5. This region of DNA m ay function as a liver-specific enhancer for the entire apoE/C-I/C-II gene cluster.