Human Molecular Genetics Advance Access originally published online on January 18, 2006
Human Molecular Genetics 2006 15(5):705-716; doi:10.1093/hmg/ddi484
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Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus
1Departments of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, USDA Children's Nutrition Research Center, Houston, TX 77030-2600, USA and 2Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA
* To whom correspondence should be addressed at: Baylor College of Medicine, USDA Children's Nutrition Research Center, 1100 Bates Street, Ste 5080, Houston, TX 77030-2600, USA. Tel: +1 7137980304; Fax: +1 7137987101; Email: waterland{at}bcm.edu
Received December 13, 2005; Accepted January 12, 2006
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/6JxCast/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 
10% of total expression after 60 days on the natural control diet. By 60 days 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-day ‘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 days 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 of Igf2, suggesting that childhood diet could contribute to IGF2 LOI in humans.
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