title: Methylated microRNA genes of the developing murine palate.
abstract: Environmental factors contribute to the etiology of cleft palate (CP). Environmental factors can also affect gene expression via alterations in DNA methylation suggesting a possible mechanism for the induction of CP. Identification of genes methylated during development of the secondary palate provides the basis for examination of the means by which environmental factors may adversely influence palatal ontogeny. We previously characterized the methylome of the developing murine secondary palate focusing primarily on protein- encoding genes. We now extend this study to include methylated microRNA (miRNA) genes. A total of 42 miRNA genes were found to be stably methylated in developing murine palatal tissue. Twenty eight of these were localized within host genes. Gene methylation was confirmed by pyrosequencing of selected miRNA genes. Integration of methylated miRNA gene and expression datasets identified 62 miRNAs, 69% of which were non-expressed. For a majority of genes (83%), upstream CpG islands (CGIs) were highly methylated suggesting down-regulation of CGI-associated promoters. DAVID and IPA analyses indicated that both expressed and non-expressed miRNAs target identical signaling pathways and biological processes associated with palatogenesis. Furthermore, these analyses also identified novel signaling pathways whose roles in palatogenesis remain to be elucidated. In summary, we identify methylated miRNA genes in the developing murine secondary palate, correlate miRNA gene methylation with expression of their cognate miRNA transcripts, and identify pathways and biological processes potentially mediated by these miRNAs.
authors: Ratnam S
authors: RS
authors: Seelan
authors: Partha
authors: P
authors: Mukhopadhyay
authors: Dennis R
authors: DR
authors: Warner
authors: Savitri N
authors: SN
authors: Appana
authors: .
authors: Guy N
authors: GN
authors: Brock
authors: M Michele
authors: MM
authors: Pisano
authors: Department of Molecular, Cellular and Craniofacial Biology, Birth Defects Center, ULSD, University of Louisville, 501 S. Preston Street, Suite 350, Louisville, KY 40202, USA.
authors: Robert M
authors: RM
authors: Greene
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics*; D010159:Palate / Q000196:embryology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic
chemical_list: D035683:MicroRNAs
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