title: Genomic organization of human transcription initiation complexes.
abstract: The human genome is pervasively transcribed, yet only a small fraction is coding. Here we address whether this non-coding transcription arises at promoters, and detail the interactions of initiation factors TATA box binding protein (TBP), transcription factor IIB (TFIIB) and RNA polymerase (Pol) II. Using ChIP-exo (chromatin immunoprecipitation with lambda exonuclease digestion followed by high-throughput sequencing), we identify approximately 160,000 transcription initiation complexes across the human K562 genome, and more in other cancer genomes. Only about 5% associate with messenger RNA genes. The remainder associates with non-polyadenylated non-coding transcription. Regardless, Pol II moves into a transcriptionally paused state, and TBP and TFIIB remain at the promoter. Remarkably, the vast majority of locations contain the four core promoter elements- upstream TFIIB recognition element (BREu), TATA, downstream TFIIB recognition element (BREd), and initiator element (INR)-in constrained positions. All but the INR also reside at Pol III promoters, where TBP makes similar contacts. This comprehensive and high-resolution genome-wide detection of the initiation machinery produces a consolidated view of transcription initiation events from yeast to humans at Pol II/III TATA-containing/TATA-less coding and non-coding genes.
authors.affiliation: Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Venters
authors.forename: B Franklin
authors.initials: BF
authors.lastname: Pugh
mesh_terms: D002843:Chromatin / Q000378:metabolism; D015894:Genome, Human / Q000235:genetics*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D059372:Nucleotide Motifs; D026723:Polyadenylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics; D016385:TATA Box / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D061785:Transcription Initiation, Genetic / Q000502:physiology*
chemical_list: D002843:Chromatin; D012333:RNA, Messenger; D014157:Transcription Factors; D012343:RNA, Transfer
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