IDENTIFICATION OF A NOVEL E1A RESPONSE ELEMENT IN THE MOUSE C-FOS PROMOTER

Transcriptional activation of the c-fos gene in mouse S49 cells by the adenovirus 243-amino-acid E1A protein depends on domains of E1A that are also required for transformation and that bind the cellular protein p300. Activation additionally depends on stimulation of endogenous cyclic AMP (cAMP)-dependent protein kinase by analogs or inducers of cAMP. Transient transfection assays were used to analyze the c-fos promoter for sequences that confer responsiveness to E1A. Linker substitution and point mutants revealed that transcriptional activation by E1A depended on a cAMP response element (CRE) located at -67 relative to the start site of transcription and a neighboring binding site for transcription factor YY1 located at -54. A 22-bp sequence containing the -67 CRE and the -54 YY1 site was sufficent to confer responsiveness to a minimal E1B promoter and was termed the c-fos E1A response element (ERE). Function of the c-fos ERE depended on both the CRE and the YY1 site, since mutation of either site resulted in a loss of responsiveness to E1A. These results imply a specific functional interaction between CRE-binding proteins, transcription factor YY1, and E1A in the regulation of the c-fos gene.