Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications
| Autor: | Alan Jackson, Mark A. Hanson, Graham C. Burdge, Jo Slater-Jefferies, Karen A. Lillycrop, Keith M. Godfrey |
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| Rok vydání: | 2007 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
medicine.medical_specialty Methyl-CpG-Binding Protein 2 Offspring Medicine (miscellaneous) Fetal Nutrition Disorders DNA methyltransferase Article Epigenesis Genetic Umbilical Cord Fetal Development Histones Receptors Glucocorticoid Glucocorticoid receptor Pregnancy Internal medicine Diet Protein-Restricted medicine Animals DNA (Cytosine-5-)-Methyltransferases Epigenetics Rats Wistar Promoter Regions Genetic Nutrition and Dietetics biology Gene Expression Regulation Developmental Acetylation Promoter Maternal Nutritional Physiological Phenomena Methylation DNA Methylation Rats Histone Endocrinology Liver Prenatal Exposure Delayed Effects DNA methylation biology.protein Female |
| Zdroj: | British Journal of Nutrition. 97:1064-1073 |
| ISSN: | 1475-2662 0007-1145 |
| DOI: | 10.1017/s000711450769196x |
| Popis: | Prenatal nutritional constraint induces an altered metabolic phenotype in the offspring which in humans confers an increased risk of non-communicable disease. Feeding a protein-restricted (PR) diet to pregnant rats causes hypomethylation of specific gene promoters in the offspring and alters the phenotype. We investigated how altered epigenetic regulation of the hepatic glucocorticoid receptor (GR) 110promoter is induced in the offspring. Rats were fed a control (180 g casein/kg) or a PR (90 g casein/kg) diet throughout pregnancy, and chow during lactation. Offspring were killed at postnatal day 34 (n5 per maternal dietary group). Methylation-sensitive PCR showed that GR110promoter methylation was 33 % lower (P P P 10promoter may result from lower capacity to methylate hemimethylated DNA during mitosis. Histone modifications which facilitate transcription were increased at the GR110promoter (147–921 %,P P n15), there was a 2-fold difference between the highest and lowest level of GR1-CTotalpromoter methylation. Dnmt1, but not Dnmt3a, expression predicted 49 % (P = 0·003) of the variation in GR1-CTotalpromoter methylation. These findings suggest that induction in the offspring of altered epigenetic regulation of the hepatic GR110promoter, and hence metabolic phenotype, may be due to reduced Dnmt1 expression. |
| Databáze: | OpenAIRE |
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