Adenovirus E1A243 disrupts the ATF/CREB-YY1 complex at the mouse c-fos promoter

The adenovirus E1A243 protein can activate transcription of the mouse c-fos gene in a manner that depends on treatment of cells with inducers or analogs of cyclic AMP (cAMP). Activation requires conserved region 1 and the N-terminal domain of E1A243 and is mediated by a 22-bp E1A response element containing a cAMP response element (CRE) at -67 and a binding site for transcription factor YY1 at -54. In the absence of E1A243, YY1 represses CRE-dependent transcription of c-fos by physically interacting with ATF/CREB proteins bound to the -67 CRE. Here we present evidence that expression of E1A243 leads to relief of YY1-mediated repression by a disruption of the ATF/CREB-YY1 complex. Addition of E1A243 to in vitro binding assays prevented binding of ATF-2 to glutathione S-transferase-YY1. Similarly, expression of E1A243 in HeLa cells prevented the association of a YY1-VP16 fusion protein with endogenous ATF/CREB proteins bound to the -67 CRE of a transfected c-fosCAT reporter plasmid. In each case, the N-terminal domain of E1A243, 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 transcriptional activation of the c-fos gene by E1A243 and cAMP.