Lsh, chromatin remodeling family member, modulates genome-wide cytosine methylation patterns at nonrepeat sequences

Proc Natl Acad Sci U S A. 2011 Apr 5;108(14):5626-31. doi: 10.1073/pnas.1017000108. Epub 2011 Mar 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Southern
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromatography, High Pressure Liquid
  • Cytosine / metabolism*
  • DNA Helicases / metabolism*
  • DNA Methylation*
  • Epigenomics*
  • Gene Expression Profiling
  • Genomics
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Statistics, Nonparametric


  • Cytosine
  • DNA Helicases
  • lymphoid specific helicase, mouse