SCAVENGER RECEPTOR-A GENE REGULATORY ELEMENTS TARGET GENE-EXPRESSION TO MACROPHAGES AND TO FOAM CELLS OF ATHEROSCLEROTIC LESIONS

Transcription of the macrophage scavenger receptor A gene is markedly upregulated during monocyte to macrophage differentiation. In these st udies, we demonstrate that 291 bp of the proximal scavenger receptor p romoter, in concert with a 400-bp upstream enhancer element, is suffic ient to direct macrophage specific expression of a human growth hormon e reporter in transgenic mice, These regulatory elements, which contai n binding sites for PU.1, AP-1, and cooperating ets-domain transcripti on factors, are also sufficient to mediate regulation of transgene exp ression during the in vitro differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor, Mutation of the PU.1 binding site within the scavenger receptor promoter severely impairs transgene expression, consistent with a crucial role of PU.1 in regulating the expression of the scavenger receptor gene, The abili ty of the scavenger receptor promoter and enhancer to target gene expr ession to macrophages in vivo, including foam cells of atherosclerotic lesions, suggests that these regulatory elements will be of general u tility in the study of macrophage differentiation and function by perm itting specific modifications of macrophage gene expression.