A concise promoter region of the heart fatty acid-binding protein gene dictates tissue-appropriate expression

The heart fatty acid-binding protein (HFABP) is a member of a family of bin ding proteins with distinct tissue distributions and diverse roles in fatty acid metabolism, trafficking, and signaling. Other members of this family have been shown to possess concise promoter regions that direct appropriate tissue-specific expression. The basis for the specific expression of the H FABP has not been previously evaluated, and the mechanisms governing expres sion of metabolic genes in the heart are not completely understood. We used transient and permanent transfections in ventricular myocytes, skeletal my ocytes, and nonmyocytic cells to map regulatory elements in the HFABP promo ter, and audited results in transgenic mice. Appropriate tissue-specific ex pression in cell culture and in transgenic mice was dictated by 1.2 kb of t he 5'-flanking sequence of FABP3, the HFABP gene. Comparison of orthologous murine and human genomic sequences demonstrated multiple regions of near-i dentity within this promoter region, including a CArG-like element close to the TATA box. Binding and transactivation studies demonstrated that this e lement can function as an atypical myocyte enhancer-binding factor 2 site. Interactions with adjacent sites are likely to be necessary for fully appro priate, tissue-specific, developmental and metabolic regulation.