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

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 hi...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2011-04, Vol.108 (14), p.5626-5631
Main Authors: Tao, Yongguang, Xi, Sichuan, Shan, Jigui, Maunakea, Alika, Che, Anney, Briones, Victorino, Lee, Eunice Y, Geiman, Theresa, Huang, Jiaqiang, Stephens, Robert, Leighty, Robert M, Zhao, Keji, Muegge, Kathrin
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Blotting, Southern
Cell Line
Chromatin
Chromatin Immunoprecipitation
Chromatin remodeling
Chromatography, High Pressure Liquid
Chromosome deletion
CpG islands
Cytosine
Cytosine - metabolism
Data processing
Deoxyribonucleic acid
DNA
DNA Helicases - metabolism
DNA Methylation
DNA methyltransferase
Epigenetics
Epigenomics
Gene expression
Gene Expression Profiling
Gene regulation
Genes
Genomes
Genomics
Methylation
methyltransferases
Mice
Mice, Knockout
normal distribution
Oligonucleotide Array Sequence Analysis
Promoter regions
repetitive sequences
Statistics, Nonparametric
Stem cells
Transcription
transcription (genetics)
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Summary: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.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1017000108