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

  1. Author:
    Tao, Y. G.
    Xi, S. C.
    Shan, J. G.
    Maunakea, A.
    Che, A.
    Briones, V.
    Lee, E. Y.
    Geiman, T.
    Huang, J. Q.
    Stephens, R.
    Leighty, R. M.
    Zhao, K. J.
    Muegge, K.

  2. Author Address

    [Tao, YG Tao, YG; Xi, SC; Briones, V; Lee, EY; Geiman, T; Huang, JQ; Muegge, K] NCI, Basic Sci Program, Lab Canc Prevent, Frederick, MD 21702 USA [Shan, JG; Che, A; Stephens, R] NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA [Leighty, RM] NCI, Data Management Serv, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA [Maunakea, A; Zhao, KJ] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20817 USA;Muegge, K (reprint author), NCI, Basic Sci Program, Lab Canc Prevent, Frederick, MD 21702 USA;Kathrin.Muegge@nih.gov
    1. Year: 2011
    2. Date: Apr
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 108
    2. 14
    3. Pages: 5626-5631
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. 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.

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External Sources

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  2. DOI: 10.1073/pnas.1017000108
  3. View record in Web of Science®
  4. WOS: 000289265300030

Library Notes

  1. Fiscal Year: FY2010-2011
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