Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development

Department of Pediatrics, Baylor College of Medicine, USDA Children's Nutrition Research Center, 1100 Bates St., Ste. 5080, Houston, TX 77030, USA.
Human Molecular Genetics (Impact Factor: 6.39). 06/2009; 18(16):3026-38. DOI: 10.1093/hmg/ddp241
Source: PubMed


The question of whether DNA methylation contributes to the stabilization of gene expression patterns in differentiated mammalian tissues remains controversial. Using genome-wide methylation profiling, we screened 3757 gene promoters for changes in methylation during postnatal liver development to test the hypothesis that developmental changes in methylation and expression are temporally correlated. We identified 31 genes that gained methylation and 111 that lost methylation from embryonic day 17.5 to postnatal day 21. Promoters undergoing methylation changes in postnatal liver tended not to be associated with CpG islands. At most genes studied, developmental changes in promoter methylation were associated with expression changes, suggesting both that transcriptional inactivity attracts de novo methylation, and that transcriptional activity can override DNA methylation and successively induce developmental hypomethylation. These in vivo data clearly indicate a role for DNA methylation in mammalian differentiation, and provide the novel insight that critical windows in mammalian developmental epigenetics extend well beyond early embryonic development.

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    • "To determine whether the suckling period might be a critical period for developmental epigenetics in the hypothalamus, we tested for changes in hypothalamic DNA methylation. We used MSAM, which is based on sequential digestion of genomic DNA with the methylation-sensitive and -insensitive isoschizomers SmaI and XmaI (23,33). Two independent P21 vs. P0 MSAM cohybridizations (incorporating a dye swap) were performed. "
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    • "The DNA methylation status has been considered to be relatively stable except during embryogenesis and carcinogenesis. However, recent studies showed that DNA methylation can be modulated in normal tissues even after birth (28). In this study, we show that expression of Gpam, which encodes a rate-limiting enzyme for TG biosynthesis, increases in the liver during weaning in response to the physiologic demand of TG biosynthesis. "
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    • "These findings emphasize the point that simply measuring fractional methylation of a gene only provides very limited in-sight into the pathways involved. Furthermore, there is not a close relationship between changes in methylation status and genes expression during development, at least in the rodent liver (Waterland et al., 2009). "
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