TFIIB recognition elements control the TFIIA-NC2 axis in transcriptional regulation.
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.
Deng
Wensheng
W
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Malecová
Barbora
B
Oelgeschläger
Thomas
T
Roberts
Stefan G E
SG
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
D010750:Phosphoproteins; D035561:Transcription Factor TFIIA; D035581:Transcription Factor TFIIB; D014157:Transcription Factors; C075995:down-regulator of transcription 1