Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

BMC Genomics

Research Article

Raoul Frijters¹  Wilco Fleuren¹  Jacob de Vlieg²  Holger M Reichardt³  Marie-Jose van Lierop⁴  Erik JM Toonen⁴  Andrea van Elsas⁴  Wim Dokter⁴  Wynand Alkema⁵  Hans van der Maaden⁶  Jan P Tuckermann⁷ 

[1] Computational Drug Discovery (CDD), Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 26-28, 6525, Nijmegen, GA, the Netherlands;Computational Drug Discovery (CDD), Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 26-28, 6525, Nijmegen, GA, the Netherlands;Department of Molecular Design & Informatics, Schering-Plough, Molenstraat 110, 5342, Oss, CC, the Netherlands;Department of Cellular and Molecular Immunology, University of Göttingen Medical School, Humboldtallee 34, 37073, Göttingen, Germany;Department of Immunotherapeutics, Schering-Plough, Molenstraat 110, 5342, Oss, CC, the Netherlands;Department of Molecular Design & Informatics, Schering-Plough, Molenstraat 110, 5342, Oss, CC, the Netherlands;Molecular Pharmacology Department, Schering-Plough, Molenstraat 110, 5342, Oss, CC, the Netherlands;Tuckermann Lab, Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstraße 11, 07745, Jena, Germany;

关键词: Prednisolone;    Wild Type Mouse;    Prednisolone Treatment;    Foxo Transcription Factor;    Dual Specificity Phosphatase;   

DOI  :  10.1186/1471-2164-11-359

 received in 2010-02-05, accepted in 2010-06-05,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGlucocorticoids (GCs) control expression of a large number of genes via binding to the GC receptor (GR). Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT) and mice that have lost the ability to form GR dimers (GRdim).ResultsThe GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization.ConclusionsThis study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

【 授权许可】

Unknown   
© Frijters et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.