title: TFIIB recognition elements control the TFIIA-NC2 axis in transcriptional regulation.
abstract: TFIIB recognizes DNA sequence-specific motifs that can flank the TATA elements of the promoters of protein-encoding genes. The TFIIB recognition elements (BRE(u) and BRE(d)) can have positive or negative effects on transcription in a promoter context-dependent manner. Here we show that the BREs direct the selective recruitment of TFIIA and NC2 to the promoter. We find that TFIIA preferentially associates with BRE-containing promoters while NC2 is recruited to promoters that lack consensus BREs. The functional relevance of the BRE-dependent recruitment of TFIIA and NC2 was determined by small interfering RNA-mediated knockdown of TFIIA and NC2, both of which elicited BRE-dependent effects on transcription. Our results confirm the established functional reciprocity of TFIIA and NC2. However, our findings show that TFIIA assembly at BRE-containing promoters results in reduced transcriptional activity, while NC2 acts as a positive factor at promoters that lack functional BREs. Taken together, our results provide a basis for the selective recruitment of TFIIA and NC2 to the promoter and give new insights into the functional relationship between core promoter elements and general transcription factor activity.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Deng
authors.forename: Barbora
authors.initials: B
authors.lastname: Malecová
authors.forename: Thomas
authors.initials: T
authors.lastname: Oelgeschläger
authors.forename: Stefan G E
authors.initials: SG
authors.lastname: Roberts
mesh_terms: D002460:Cell Line; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D035561:Transcription Factor TFIIA / Q000235:genetics / Q000378:metabolism*; D035581:Transcription Factor TFIIB / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D010750:Phosphoproteins; D035561:Transcription Factor TFIIA; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; C075995:down-regulator of transcription 1