title: Requirement for transcription factor IIA (TFIIA)-TFIID recruitment by an activator depends on promoter structure and template competition.
abstract: Different mechanisms of transcriptional activation may be required for distinct classes of promoters and cellular conditions. The Epstein-Barr virus (EBV)-encoded transcriptional activator Zta recruits the general transcription factors IID (TFIID) and IIA (TFIIA) to promoter DNA and induces a TATA box-binding protein (TBP)-associated factor-dependent footprint downstream of the transcriptional initiation site. In this study, we investigated the functional significance of TFIID-TFIIA (D-A complex) recruitment by Zta. Alanine substitution mutations in the Zta activation domain which eliminate the ability of Zta to stimulate the D-A complex were examined. These Zta mutants were defective in the ability to activate transcription from an EBV-derived promoter (BHLF1) but activated a highly responsive synthetic promoter (Z7E4T). Both the number of activator binding sites and the core promoter region contribute to the requirement for D-A complex recruitment. These functionally distinct core promoters had significant differences in affinity for TBP and TFIID binding. The D-A complex-recruiting activity of Zta was found to be important for promoter selection in the presence of a competitor template. Conditions which limit TFIID binding to the TATA element or compromise the ability of TFIIA to bind TBP required activator stimulation of the D-A complex. These results indicate that D-A complex recruitment is one of at least two activation pathways utilized by Zta and is the essential pathway for a subset of promoters and conditions which limit TFIID binding to the TATA element.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania 19104, USA. lieberman@wista.wistar.upenn.edu
authors.forename: P M
authors.initials: PM
authors.lastname: Lieberman
authors.forename: J
authors.initials: J
authors.lastname: Ozer
authors.forename: D B
authors.initials: DB
authors.lastname: Gürsel
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D009154:Mutation; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016385:TATA Box; D035181:TATA-Box Binding Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D035561:Transcription Factor TFIIA; D035362:Transcription Factor TFIID; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D035561:Transcription Factor TFIIA; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D014764:Viral Proteins