Human Molecular Genetics Advance Access published online on January 18, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddi484
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1 Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, USDA Children's Nutrition Research Center, 1100 Bates St., Ste 5080, Houston, Texas 77030-2600, USA
* To whom correspondence should be addressed. IGF2 loss of imprinting (LOI) is fairly prevalent and implicated in the pathogenesis of human cancer and developmental disease; however, the causes of this phenomenon are largely unknown. We determined whether the post-weaning diet of mice affects allelic expression and CpG methylation of Igf2. C57BL/6J x Cast/EiJ F1 hybrid mice were weaned onto 1) a standard natural ingredient control diet, 2) a synthetic control diet, or 3) a synthetic methyl-donor deficient diet lacking folic acid, vitamin B12, methionine and choline. Maternal Igf2 expression in kidney was negligible at birth, but increased to
Received December 13, 2005
Revised January 12, 2006
Accepted January 12, 2006
Article
Post-weaning diet affects genomic imprinting at the Insulin-Like Growth Factor 2 (Igf2) locus
Robert A. Waterland 1 *,
Juan-Ru Lin 2,
Charlotte A. Smith 2,
and
Randy L. Jirtle 3
2 Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, USDA Children's Nutrition Research Center, Houston, Texas 77030-2600, USA
3 Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 USA
Robert A. Waterland, E-mail: waterland{at}bcm.edu
Abstract 
10% of total expression after 60 d on the natural control diet. By 60 d post-weaning both synthetic diets caused significant LOI of Igf2 relative to animals weaned onto the natural control diet. Total Igf2 expression was significantly reduced in these groups, however, indicating that the increase in relative maternal Igf2 expression was caused by specific down-regulation of the paternal allele. The LOI induced by the synthetic deficient diet persisted during a subsequent 100-d ‘recuperation’ period on natural ingredient diet. There were no group differences in overall or allele-specific CpG methylation in the H19 differentially methylated region (DMR), Igf2 DMR0, or Igf2 DMR1. At 30 and 60 d post-weaning, however, the paternal allele of Igf2 DMR2 was hypermethylated in the kidneys of mice on the control synthetic diet. These results indicate that post-weaning diet can permanently affect expression and methylation of Igf2, suggesting that childhood diet could contribute to IGF2 loss of imprinting in humans.
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