ADENOVIRUS E1A(243) DISRUPTS THE ATF CREB-YY1 COMPLEX AT THE MOUSE C-FOS PROMOTER/

The adenovirus E1A(243) protein can activate transcription of the mous e c-fos gene in a manner that depends on treatment of cells with induc ers or analogs of cyclic AMP (cAMP). Activation requires conserved reg ion 1 acid the N-terminal domain of E1A(243) and is mediated by a 22-b p ELA response element containing a cAMP response element (CRE) at -67 and a binding site for transcription factor YY1 at -54. In the absenc e of E1A(243), YY1 represses CRE-dependent transcription of c-fos by p hysically interacting with ATF/CREB proteins bound to the -67 CRE. Her e we present evidence that expression of E1A(243) leads to relief of Y Y1-mediated repression by a disruption of the ATF/CREB-YY1 complex. Ad dition of E1A(243) to in vitro binding assays prevented binding of ATF -2 to glutathione S-transferase-YY1. Similarly, expression of E1A(243) in HeLa cells prevented the association of a YY1-VP16 fusion protein with endogenous ATF/CREB proteins bound to the -67 CRE of a transfecte d c-fosCAT reporter plasmid. In each case, the N-terminal domain of E1 A(243), which mediates a direct interaction with YY1, was responsible for disruption of the ATF/CREB-YY1 complex. On the basis of these and previously published results, we present a model for the synergistic t ranscriptional activation of the c-fos gene by E1A(243) and cAMP.