Genomic organization of human transcription initiation complexes

Bryan J. Venters, B. Franklin Pugh

Research output: Contribution to journalArticle

45 Scopus citations

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 (BRE u), TATA, downstream TFIIB recognition element (BRE d), 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.

Original languageEnglish (US)
Pages (from-to)53-58
Number of pages6
JournalNature
Volume502
Issue number7469
DOIs
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • General

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