title: Lsh, chromatin remodeling family member, modulates genome-wide cytosine methylation patterns at nonrepeat sequences.
abstract: 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.
authors.affiliation: Basic Science Program, Laboratory of Cancer Prevention, Advanced Biomedical Computing Center, and Data Management Services, Science Applications International Corporation Frederick, Inc, National Cancer Institute Frederick, Frederick, MD 21702, USA.
authors.forename: Yongguang
authors.initials: Y
authors.lastname: Tao
authors.forename: Sichuan
authors.initials: S
authors.lastname: Xi
authors.forename: Jigui
authors.initials: J
authors.lastname: Shan
authors.forename: Alika
authors.initials: A
authors.lastname: Maunakea
authors.forename: Anney
authors.initials: A
authors.lastname: Che
authors.forename: Victorino
authors.initials: V
authors.lastname: Briones
authors.forename: Eunice Y
authors.initials: EY
authors.lastname: Lee
authors.forename: Theresa
authors.initials: T
authors.lastname: Geiman
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Huang
authors.forename: Robert
authors.initials: R
authors.lastname: Stephens
authors.forename: Robert M
authors.initials: RM
authors.lastname: Leighty
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.forename: Kathrin
authors.initials: K
authors.lastname: Muegge
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D019175:DNA Methylation; D057890:Epigenomics; D020869:Gene Expression Profiling; D023281:Genomics; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D018709:Statistics, Nonparametric
chemical_list: D003596:Cytosine; D004265:DNA Helicases; C491758:lymphoid specific helicase, mouse