Role of De Novo DNA Methyltransferases in Initiation of Genomic Imprinting and X-Chromosome Inactivation

DNA methylation is an epigenetic mechanism thatplays a key role in regulation of developmental gene expression, maintenance of genomic integrity, genomic imprinting, and X-chromosome inactivation (X-inactivation)in mammals. Methylation of mammalian genomic DNAoccurs almost exclusively at the cytosine of CpG dinucleotides. The CpG methylation pattern of the mammaliangenome is created and maintained by a combination of denovo DNA methyltransferases, Dnmt3a and Dnmt3b, anda maintenance DNA methyltransferase Dnmt1. Targeteddisruption of these DNA methyltransferase genes in miceresults in embryonic or early postnatal lethality, indicatingthat they are essential for normal mammalian development (Li et al. 1992; Okano et al. 1999)...