Multiple interdependent regulatory sites in the mouse c-fos promoter determine basal level transcription: cell type-specific effects.

Although the induction of the mouse c-fos promoter by growth factors and specific signal transduction pathways has been analyzed in some detail, the mechanisms involved in the control of basal level transcription remain largely elusive. In this study, we present evidence for the existence of at least 9 different elements, located between the putative TATA box and position -610, that figure in basal level transcription and represent protein binding sites in different cell types. A major regulatory site in F9END, NIH3T3 and HeLa cells is the CRE around position -60. Other sites, including the SRE, a NF1 site around position -165, a novel site downstream of the SRE and three new sites upstream of the SRE play different cell type-specific roles. In addition, we have identified two regions upstream of the SRE, which seem to have cell type-specific negative regulatory effects. We also find that the precise function of several of these sites depends on the presence or absence of other elements, indicating some form of interaction between different regulatory sites. Finally, we present evidence, that the block of c-fos transcription in F9EC cells is due to the lack of transregulatory proteins, which are induced during retinoic acid mediated differentiation.