Human Molecular Genetics Advance Access originally published online on May 20, 2009
Human Molecular Genetics 2009 18(16):3026-3038; doi:10.1093/hmg/ddp241
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Epigenomic profiling indicates a role for DNA methylation in early postnatal liver development
1 Department of Pediatrics 2 Department of Molecular and Human Genetics, Baylor College of Medicine, USDA Children's Nutrition Research Center, 1100 Bates St., Ste. 5080, Houston, TX 77030, USA 3 Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, TX, USA 4 Department of Biostatistics and Applied Biomathematics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA 5 Department of Computer Science, Duke University, Durham, NC, USA 6 Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
* To whom correspondence should be addressed. Tel: +1 7137980304; Fax: +1 7137987101; Email: waterland{at}bcm.edu
Received March 4, 2009; Revised April 24, 2009; Accepted May 18, 2009
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.