Nucleic Acids Research Advance Access originally published online on November 29, 2007
Nucleic Acids Research 2008 36(2):539-549; doi:10.1093/nar/gkm1078
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Nucleic Acids Research, 2008, Vol. 36, No. 2 539-549
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
The dual control of TFIIB recruitment by NC2 is gene specific
1Department of Microbiology and Molecular Medicine, CMU, 1 rue Michel Servet 1211, Geneva 4, Switzerland and 2Department of Pathology and Immunology
*To whom correspondence should be addressed. Tel: 004122 3795476; Fax: 004122 3795702; Email: martine.collart{at}medecine.unige.ch
Received October 19, 2007. Revised November 14, 2007. Accepted November 15, 2007.
Negative co-factor 2 (NC2) is a conserved eukaryotic complex composed of two subunits, NC2
(Drap1) and NC2β (Dr1) that associate through a histone-fold motif. In this work, we generated mutants of NC2, characterized target genes for these mutants and studied the assembly of NC2 and general transcription factors on target promoters. We determined that the two NC2 subunits mostly function together to be recruited to DNA and regulate gene expression. We found that NC2 strongly controls promoter association of TFIIB, both negatively and positively. We could attribute the gene-specific repressor effect of NC2 on TFIIB to the C-terminal domain of NC2β, and define that it requires ORF sequences of the target gene. In contrast, the positive function of NC2 on TFIIB targets is more general and requires adequate levels of the NC2 histone-fold heterodimer on promoters. Finally, we determined that NC2 becomes limiting for TATA-binding protein (TBP) association with a heat inducible promoter under heat stress. This study demonstrates an important positive role of NC2 for formation of the pre-initiation complex on promoters, under normal conditions through control of TFIIB, or upon activation by stress via control of TBP.
Present address: Sandrine Creton, Max Planck Institute of Biochemistry, Department of Molecular Cell Biology, Am Klopferspitz 18, 82152 Martinsried, Germany
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