Identification of a fat cell enhancer: Analysis of requirements for adipose tissue‐specific gene expression

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Abstract
The molecular basis for adipose‐specific gene expression is not known. To approach the problem of adipocyte gene expression, we have analyzed in detail the capacity of the 5′‐flanking region of the adipocyte P2 (aP2) gene to direct cell‐type specific gene expression. Although the proximal promoter containing AP‐1 and C/EBP binding sites is capable of directing differentiation‐dependent gene expression in cultured adipocytes, these constructs are essentially inactive in the tissues of transgenic mice. We found that −5.4 kb of the 5‐flanking region were required to direct heterologous gene (chloramphenicol acetyl transferase; CAT) expression to the adipose tissue of transgenic mice. By deletion analysis, we identified a 520 bp enhancer at −5.4 kb of the aP2 gene. We show that this enhancer can direct high levels of gene expression specifically to the adipose tissue of transgenic mice. This enhancer also functions in a differentiation‐dependent manner in cultured adipocytes and cannot be transactivated in preadipocytes by C/EBP. Molecular analysis indicates that several cis‐ and transacting acting elements, though not C/EBP, contribute to the specificity and potency of this enhancer.