title: DNA methylation profile of the mouse skeletal alpha-actin promoter during development and differentiation.
abstract: Genomic levels of DNA methylation undergo widespread alterations in early embryonic development. However, changes in embryonic methylation have proven difficult to study at the level of single-copy genes due to the small amount of tissue available for assay. This study provides the first detailed analysis of the methylation state of a tissue-specific gene through early development and differentiation. Using bisulfite sequencing, we mapped the methylation profile of the tissue-specific mouse skeletal alpha-actin promoter at all stages of development, from gametes to postimplantation embryos. We show that the alpha-actin promoter, which is fully methylated in the sperm and essentially unmethylated in the oocyte, undergoes a general demethylation from morula to blastocyst stages, although the blastula is not completely demethylated. Remethylation of the alpha-actin promoter occurs after implantation in a stochastic pattern, with some molecules being extensively methylated and others sparsely methylated. Moreover, we demonstrate that tissue-specific expression of the skeletal alpha-actin gene in the adult mouse does not correlate with the methylation state of the promoter, as we find a similar low level of methylation in both expressing and one of the two nonexpressing tissues tested. However, a subset of CpG sites within the skeletal alpha-actin promoter are preferentially methylated in liver, a nonexpressing tissue.
authors.affiliation: Kanematsu Laboratories, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.
authors.forename: P M
authors.initials: PM
authors.lastname: Warnecke
authors.forename: S J
authors.initials: SJ
authors.lastname: Clark
mesh_terms: D000199:Actins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D019175:DNA Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051381:Rats; D012863:Skeleton
chemical_list: D000199:Actins