title: The ets-related transcription factor GABP directs bidirectional transcription.
abstract: Approximately 10% of genes in the human genome are distributed such that their transcription start sites are located less than 1 kb apart on opposite strands. These divergent gene pairs have a single intergenic segment of DNA, which in some cases appears to share regulatory elements, but it is unclear whether these regions represent functional bidirectional promoters or two overlapping promoters. A recent study showed that divergent promoters are enriched for consensus binding sequences of a small group of transcription factors, including the ubiquitous ets-family transcription factor GA-binding protein (GABP). Here we show that GABP binds to more than 80% of divergent promoters in at least one cell type. Furthermore, we demonstrate that GABP binding is correlated and associated with bidirectional transcriptional activity in a luciferase transfection assay. In addition, we find that the addition of a strict consensus GABP site into a set of promoters that normally function in only one direction significantly increases activity in the opposite direction in 67% of cases. Our findings demonstrate that GABP regulates the majority of divergent promoters and suggest that bidirectional transcriptional activity is mediated through GABP binding and transactivation at both divergent and nondivergent promoters.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Collins
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Loan
authors.initials: L
authors.lastname: Nguyen
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Trinklein
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D051268:GA-Binding Protein Transcription Factor / Q000378:metabolism*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D051268:GA-Binding Protein Transcription Factor; D050783:Proto-Oncogene Proteins c-ets; D008156:Luciferases