title: Novel isoforms of the TFIID subunit TAF4 modulate nuclear receptor-mediated transcriptional activity.
abstract: The transcription factor TFIID consists of TATA-binding protein (TBP) and TBP-associated factors (TAFs). TAFs are essential for modulation of transcriptional activity but the regulation of TAFs is complex and many important aspects remain unclear. In this study, we have identified and characterized five novel truncated forms of the TFIID subunit TAF4 (TAF(II)135). Analysis of the mouse gene structure revealed that all truncations were the results of alternative splicing and resulted in the loss of domains or parts of domains implicated in TAF4 functional interactions. Results from transcriptional assays showed that several of the TAF4 isoforms exerted dominant negative effects on TAF4 activity in nuclear receptor-mediated transcriptional activation. In addition, alternative TAF4 isoforms could be detected in specific cell types. Our results indicate an additional level of complexity in TAF4-mediated regulation of transcription and suggest context-specific roles for these new TAF4 isoforms in transcriptional regulation in vivo.
authors.affiliation: Group of Transcriptional Networks, Unit of Functional Genomics, Center for Genomics and Bioinformatics (CGB), Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Adrian
authors.initials: A
authors.lastname: Brunkhorst
authors.forename: Toomas
authors.initials: T
authors.lastname: Neuman
authors.forename: Anita
authors.initials: A
authors.lastname: Hall
authors.forename: Ernest
authors.initials: E
authors.lastname: Arenas
authors.forename: Tamas
authors.initials: T
authors.lastname: Bartfai
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
authors.forename: Madis
authors.initials: M
authors.lastname: Metsis
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D040481:Genome Components / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms; D021122:Protein Subunits; D018168:Receptors, Retinoic Acid / Q000378:metabolism* / Q000502:physiology; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D020033:Protein Isoforms; D021122:Protein Subunits; D018168:Receptors, Retinoic Acid; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D000242:Cyclic AMP