Basal core promoters control the equilibrium between negative cofactor 2 and preinitiation complexes in human cells.
Genome Biol
; 11(3): R33, 2010.
Article
in En
| MEDLINE
| ID: mdl-20230619
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
Transcription Factors
/
RNA Polymerase II
/
Promoter Regions, Genetic
/
TATA-Box Binding Protein
/
Transcription Factor TFIIB
/
Multiprotein Complexes
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Genome Biol
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA
Year:
2010
Type:
Article
Affiliation country:
Germany