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.
D051696:Activating Transcription Factors; D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D016762:Genes, fos; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D050986:YY1 Transcription Factor; D016335:Zinc Fingers
D051696:Activating Transcription Factors; D017500:Adenovirus E1A Proteins; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494699:Yy1 protein, mouse; D000242:Cyclic AMP