Nucleic Acids Research Advance Access originally published online on July 10, 2007
Nucleic Acids Research 2007 35(14):4858-4868; doi:10.1093/nar/gkm492
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Nucleic Acids Research, 2007, Vol. 35, No. 14 4858-4868
© 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 |
Elk1 and SRF transcription factors convey basal transcription and mediate glucose response via their binding sites in the human LXRB gene promoter
Department of Biosciences and Nutrition at Novum, Karolinska Institutet, S-14157 Huddinge, Sweden
*To whom correspondence should be addressed. Tel: +46 8 608 33 39; Fax: +46 8 774 55 38; Email: knut.steffensen{at}biosci.ki.se
Received March 27, 2007. Revised June 1, 2007. Accepted June 6, 2007.
The nuclear receptors LXR
(NR1H3) and LXRß (NR1H2) are attractive drug targets for the treatment of diabetes and cardiovascular disease due to their established role as regulators of cholesterol and lipid metabolism. A large body of literature has recently indicated their important roles in glucose metabolism and particularly LXRß is important for proper insulin production in pancreas. In this study, we report that glucose induces transcription via the LXRB gene promoter. The transcription start site of the human LXRB gene was determined and we identified two highly conserved, and functional, ETS and Elk1 binding sites, respectively, in the LXRB gene promoter. The Elk1 binding site also bound the serum responsive factor (SRF). Mutation of these sites abolished binding. Furthermore, mutation of the binding sites or siRNA knockdown of SRF and Elk1 significantly reduced the promoter activity and impaired the glucose response. Our results indicate that the human LXRB gene is controlled by glucose, thereby providing a novel mechanism by which glucose regulates cellular functions via LXRß.