CELL-SPECIFIC EXPRESSION OF THE MACROPHAGE SCAVENGER RECEPTOR GENE ISDEPENDENT ON PU.1 AND A COMPOSITE AP-1 ETS MOTIF

The type I and II scavenger receptors (SRs) are highly restricted to c ells of monocyte origin and become maximally expressed during the proc ess of monocyte-to-macrophage differentiation. In this report, we pres ent evidence that SR genomic sequences from -245 to +46 bp relative to the major,transcriptional start site were sufficient to confer prefer ential expression of a reporter gene to cells of monocyte and macropha ge origin. This profile of expression resulted from the combinatorial actions of multiple positive and negative regulatory elements. Positiv e transcriptional control was primarily determined by two elements, lo cated 181 and 46 bp upstream of the major transcriptional start site. Transcriptional control via the -181 element was mediated by PUI.1/Spi -1, a macrophage and B-cell-specific transcription factor that is a me mber of the ets domain gene family. Intriguingly, the -181 element rep resented a relatively low-sanity binding site for Spi-B, a closely rel ated member of the ets domain family that has been shown to bind with relatively high affinity to other PU.1/Spi-1 binding sites. These obse rvations support the idea that PU.1/Spi-1 and Spi-B regulate overlappi ng but nonidentical sets of genes. The -46 element represented a compo site binding site for a distinct set of ets domain proteins that were preferentially expressed in monocyte and macrophage cell lines acid th at formed ternary complexes with members of the AP-1 gene family. In c oncert, these observations suggest a model for how interactions betwee n cell-specific and more generally expressed transcription factors fun ction to dictate the appropriate temporal and cell-specific patterns o f SR expression during the process of macrophage differentiation.