Location: Children's Nutrition Research CenterTitle: Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development) Author
Submitted to: Human Molecular Genetics
Publication Type: Peer reviewed journal
Publication Acceptance Date: 5/18/2009
Publication Date: 5/20/2009
Citation: Waterland, R., Kellermayer, R., Rached, M., Tatevian, N., Gomes, M.V., Zhang, J., Zhang, L., Chakravarty, A., Zhu, W., Laritsky, E., Zhang, W., Wang, X., Shen, L. 2009. Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development. Human Molecular Genetics. 18(16):3026-3038. Interpretive Summary: During postnatal life, the liver undergoes developmental maturation, meaning it gradually begins to express different genes to prepare it for the metabolic demands of adulthood. This study evaluated the role of DNA methylation in mediating these developmental changes in gene expression. DNA methylation is the addition of a methyl (CH3) group to cytosine, of one of the base “building blocks” of DNA. This modification provides an additional level of information, above the DNA sequence information. Our study identified genes that undergo changes in DNA methylation in mouse liver DNA from late fetal life to early postnatal (age 21 days). We found that changes in DNA methylation are usually correlated with changes in gene expression in the liver, indicating that developmental changes in DNA methylation are somehow contributing to the stable regulation of developmental changes in gene expression.
Technical Abstract: 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.