Premium
DNA methylation of the Liver X‐Receptor (LXR) gene promoter in the fetal mouse liver
Author(s) -
Plosch Torsten,
Straten Esther M.E.,
Bloks Vincent W.,
Huijkman Nicolette C.A.,
Kuipers Folkert
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.717.2
Prenatal nutrition has been epidemiologically identified as a determinant of adult disease. We hypothesized that maternal protein restriction would induce epigenetic adaptations that would interfere with lipid metabolism and hence predispose to atherosclerosis. C57BL/6 mice were fed a protein restricted diet during pregnancy. CpG island methylation microarrays were performed on fetal liver DNA on day 19.5 of pregnancy. 204 gene promoter regions were found to be differentially methylated upon protein restriction. Hyper methylation and hypo methylation were found in comparable numbers. The liver X‐receptor (Lxr) alpha promoter was hypermethylated in protein‐restricted pups. In parallel, the mRNA level of Lxra was reduced by 32% in fetal liver upon maternal protein restriction. Lxr alpha is a nuclear receptor critically involved in control of cholesterol and fatty acid metabolism. In vitro methylation of a mouse Lxra‐promoter/luciferase expression cassette resulted in a 24‐fold transcriptional Lxr repression. Our study demonstrates that Lxra is a new target of differential DNA methylation. We speculate that changes in DNA methylation contribute to the relationship between early nutrition and adult disease. Supported by the Netherlands Heart Foundation, grant 2004T048 to T.P.