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Genome Biol. 2010;11(3):R33. doi: 10.1186/gb-2010-11-3-r33. Epub 2010 Mar 15.

Basal core promoters control the equilibrium between negative cofactor 2 and preinitiation complexes in human cells.

Author information

1
Institute of Molecular Tumor Biology (IMTB), University of Muenster, Robert-Koch-Str, Muenster, Germany. albertt@uni-muenster.de

Abstract

BACKGROUND:

The general transcription factor TFIIB and its antagonist negative cofactor 2 (NC2) are hallmarks of RNA polymerase II (RNAPII) transcription. Both factors bind TATA box-binding protein (TBP) at promoters in a mutually exclusive manner. Dissociation of NC2 is thought to be followed by TFIIB association and subsequent preinitiation complex formation. TFIIB dissociates upon RNAPII promoter clearance, thereby providing a specific measure for steady-state preinitiation complex levels. As yet, genome-scale promoter mapping of human TFIIB has not been reported. It thus remains elusive how human core promoters contribute to preinitiation complex formation in vivo.

RESULTS:

We compare target genes of TFIIB and NC2 in human B cells and analyze associated core promoter architectures. TFIIB occupancy is positively correlated with gene expression, with the vast majority of promoters being GC-rich and lacking defined core promoter elements. TATA elements, but not the previously in vitro defined TFIIB recognition elements, are enriched in some 4 to 5% of the genes. NC2 binds to a highly related target gene set. Nonetheless, subpopulations show strong variations in factor ratios: whereas high TFIIB/NC2 ratios select for promoters with focused start sites and conserved core elements, high NC2/TFIIB ratios correlate to multiple start-site promoters lacking defined core elements.

CONCLUSIONS:

TFIIB and NC2 are global players that occupy active genes. Preinitiation complex formation is independent of core elements at the majority of genes. TATA and TATA-like elements dictate TFIIB occupancy at a subset of genes. Biochemical data support a model in which preinitiation complex but not TBP-NC2 complex formation is regulated.

PMID:
20230619
PMCID:
PMC2864573
DOI:
10.1186/gb-2010-11-3-r33
[Indexed for MEDLINE]
Free PMC Article

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