Methylation patterns of the mammalian genome are crucial for normal embryonic development. DNA methylation regulates diverse biologic processes such as genomic imprinting and X chromosome inactivation. The precise mechanisms designating specific genomic loci for methylation are not well understood. Lsh is a member of the SNF2 family of chromatin remodelers. Targeted deletion of Lsh results in perinatal lethality with a rather normal development. However, Lsh-/- mice show substantial loss of methylation throughout the genome. Repetitive elements as well as single-copy genes are hypomethylated. This suggests that global genomic methylation is not absolutely required for normal embryogenesis. The presumed chromatin remodeling activity of Lsh suggests that alteration of chromatin affects global methylation patterns in mice.