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 protei n p300. Activation additionally depends on stimulation of endogenous c yclic AMP (cAMP)-dependent protein kinase by analogs or inducers of cA MP. Transient transfection assays were used to analyze the c-fos promo ter for sequences that confer responsiveness to E1A. Linker substituti on and point mutants revealed that transcriptional activation by E1A d epended on a cAMP response element (CRE) located at -67 relative to th e start site of transcription and a neighboring binding site for trans cription factor YY1 located at -54. A 22-bp sequence containing the -6 7 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 (E RE). Function of the c-fos ERE depended on both the CRE and the YY1 si te, 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 regula tion of the c-fos gene.