In this study we have identified a strong distal enhancer of ADH4 that displays some cell specificity. Undoubtedly, transient transfection assays cannot duplicate the regulatory complexity present in vivo, including additional cis-regulatory regions and complexity of chromatin structure. However, in the genome-wide mapping of DNase I hypersensitive sites in HepG2 cells, a hypersensitive peak was detected across the region of five transcription factor binding sites that we characterized in this enhancer (UCSC Open chromatin track; (Boyle et al., 2008). This suggests that the site we identified is occupied by transcription factors and functional in vivo; whether this enhancer is sufficient to drive the expression of ADH4 remains to be tested. Our haplotype studies indicate that variations in this region will contribute to differences in ADH4 expression. It would be of interest to study if these variations will contribute to differential susceptibility to alcoholism.
