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Induction of c-fos by cyclic AMP in NIH-3T3 cells is distinct from induction by serum. Whereas induction by serum is mediated by the serum response element (SRE), induction by cAMP does not require this element. In fact, no single sequence element in the c-fos promoter/enhancer is stringently required for the cAMP response. Rather, multiple sequence elements in the c-fos promoter/enhancer can mediate induction by cAMP independently. These elements are: (1) the region from -72 to -54, which contains a binding site for a cellular activating transcription factor (ATF); (2) the region from -225 to -99; (3) the region from -303 to -281, which is homologous to the consensus binding site for the transcription factor AP1; and (4) the region from -317 to -298, which contains the SRE. These sequence elements convey cAMP inducibility when fused to the cAMP-unresponsive 'minimal' fos promoter (-53 to +42). In addition, the c-fos regions from -700 to -63 and from -71 to -48 can confer cAMP inducibility to a heterologous promoter.

Multiple sequence elements in the c-fos promoter mediate induction by cAMP.