Allele-specific non-CpG methylation of the Nf1 gene during early mouse development.
Recent reports of cytosine methylation occurring at CpA and CpT dinucleotides in murine ES cells as well as in Drosophila have renewed interest in methylation at sites other than CpGs. Our examination of the murine neurofibromatosis type 1 gene by sodium bisulfite genomic sequencing has revealed non-CpG methylation primarily in the oocyte and the maternally derived allele of the 2-cell embryo, with markedly lower levels found in sperm. Non-CpG methylation was not found in later stages of embryo development or in adult tissue. Our results suggest that maternal-specific de novo non-CpG methylation has occurred sometime between ovulation and formation of the 2-cell embryo, while during the same period the paternally derived allele has undergone site-specific active demethylation. Our data demonstrate both stage and parent-of-origin specific changes in methylation patterns within the neurofibromatosis type 1 coding region-involving cytosines located at both CpG and non-CpG dinucleotides.
Haines
T R
TR
London Regional Cancer Centre, Departments of Biochemistry, Child Health Research Institute, London Health Sciences Centre, Ontario, London, N6C 2V5, Canada.
Rodenhiser
D I
DI
Ainsworth
P J
PJ
D000243:Adenosine Deaminase / Q000235:genetics; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002970:Cleavage Stage, Ovum / Q000378:metabolism; D018899:CpG Islands; D003433:Crosses, Genetic; D004247:DNA / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009115:Muridae; D009865:Oocytes / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013094:Spermatozoa / Q000378:metabolism
D004247:DNA; D000243:Adenosine Deaminase