Comprehensive genomic map of cytosine methylation for wild-type (WT) and Lsh-/- mouse embryonic fibroblasts. Mus musculus

DNA methylation is critical for normal development and plays important roles in genome organization and transcriptional regulation. Although DNA methyltransferases have been identified, the factors that establish and contribute to genome-wide methylation patterns remain elusive. Here, we report a high-resolution cytosine methylation map of the murine genome modulated by Lsh, a chromatin remodeling family member that has previously been shown to regulate CpG methylation at repetitive sequences. We provide evidence that Lsh also controls genome-wide cytosine methylation at nonrepeat sequences and relate those changes to alterations in H4K4me3 modification and gene expression. Deletion of Lsh alters the allocation of cytosine methylation in chromosomal regions of 50 kb to 2 Mb and, in addition, leads to changes in the methylation profile at the 5′ end of genes. Furthermore, we demonstrate that loss of Lsh promotes—as well as prevents—cytosine methylation. Our data indicate that Lsh is an epigenetic modulator that is critical for normal distribution of cytosine methylation throughout the murine genome. We used microarrays to detail a high-resolution cytosine methylation map of the murine genome modulated by Lsh, a chromatin remodeling family member that has previously been shown to regulate CpG methylation at repetitive sequences Overall design: To investigate how genome-wide DNA methylation patterns are established in mice and how they may specifically depend on Lsh, we generated a comprehensive genomic map of cytosine methylation for wild-type (WT) and Lsh−/− mouse embryonic fibroblasts (MEFs) using methylated DNA immunoprecipitation (MeDIP) combined with whole-genome tiling microarray. In addition, we generated a histone 3 lysine 4 trimethylation (H3K4me3) chromatin map using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) and also evaluated genome-wide gene expression using cDNA microarrays