Nucleic Acids Research Advance Access published online on September 29, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp804
Gene Regulation, Chromatin and Epigenetics |
Overlapping promoter targeting by Elk-1 and other divergent ETS-domain transcription factor family members
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK
*To whom correspondence should be addressed. Tel: +44 161 275 5979; Fax: +44 161 275 5082; Email: a.d.sharrocks{at}manchester.ac.uk
Received June 29, 2009. Revised September 10, 2009. Accepted September 11, 2009.
ETS-domain transcription factors play important roles in controlling gene expression in a variety of different contexts; however, these proteins bind to very similar sites and it is unclear how in vivo specificity is achieved. In silico analysis is unlikely to reveal specific targets for individual family members and direct experimental approaches are therefore required. Here, we take advantage of an inducible dominant-negative expression system to identify a group of novel target genes for the ETS-domain transcription factor Elk-1. Elk-1 is thought to mainly function through cooperation with a second transcription factor SRF, but the targets we identify are largely SRF-independent. Furthermore, we demonstrate that there is a high degree of overlapping, cell type-specific, target gene binding by Elk-1 and other ETS-domain transcription factors. Our results are therefore consistent with the notion that there is a high degree of functional redundancy in target gene regulation by ETS-domain transcription factors in addition to the specific target gene regulation that can be dictated through heterotypic interactions exemplified by the Elk-1-SRF complex.
Present address: Aneta Kasza, Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Krakow, Poland.