Genomic organization of human transcription initiation complexes

Bryan J. Venters, B. Franklin Pugh

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 - Sep 24 2013

Fingerprint

Transcription Factor TFIIB
TATA-Box Binding Protein
Human Genome
Genome
Peptide Initiation Factors
Exonucleases
RNA Polymerase II
Chromatin Immunoprecipitation
Genes
Digestion
Yeasts
Messenger RNA
Neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • General

Cite this

Venters, Bryan J. ; Pugh, B. Franklin. / Genomic organization of human transcription initiation complexes. In: Nature. 2013 ; Vol. 502, No. 7469. pp. 53-58.
@article{ce2934d1094443949d1ba42aa720bd69,
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 (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.",
author = "Venters, {Bryan J.} and Pugh, {B. Franklin}",
year = "2013",
month = "9",
day = "24",
doi = "10.1038/nature12535",
language = "English (US)",
volume = "502",
pages = "53--58",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7469",

}

Genomic organization of human transcription initiation complexes. / Venters, Bryan J.; Pugh, B. Franklin.

In: Nature, Vol. 502, No. 7469, 24.09.2013, p. 53-58.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genomic organization of human transcription initiation complexes

AU - Venters, Bryan J.

AU - Pugh, B. Franklin

PY - 2013/9/24

Y1 - 2013/9/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84885607335&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885607335&partnerID=8YFLogxK

U2 - 10.1038/nature12535

DO - 10.1038/nature12535

M3 - Article

C2 - 24048476

AN - SCOPUS:84885607335

VL - 502

SP - 53

EP - 58

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7469

ER -