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Impact of chromatin structure on sequence variability in the human genome

  1. Author:
    Tolstorukov, M. Y.
    Volfovsky, N.
    Stephens, R. M.
    Park, P. J.

  2. Author Address

    [Tolstorukov, Michael Y.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Tolstorukov, Michael Y.; Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Volfovsky, Natalia; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick, Frederick, MD 21701 USA. [Park, Peter J.] Childrens Hosp Boston, HST Informat Program, Boston, MA USA.;Park, PJ, Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA.;peter_park@harvard.edu
    1. Year: 2011
    2. Date: Apr
  2. Journal: Nature Structural & Molecular Biology
    1. 18
    2. 4
    3. Pages: 510-U152
  4. Type of Article: Article
  5. ISSN: 1545-9985
  1. Abstract:

    DNA sequence variations in individual genomes give rise to different phenotypes within the same species. One mechanism in this process is the alteration of chromatin structure due to sequence variation that influences gene regulation. We composed a high-confidence collection of human single-nucleotide polymorphisms and indels based on analysis of publicly available sequencing data and investigated whether the DNA loci associated with stable nucleosome positions are protected against mutations. We addressed how the sequence variation reflects the occupancy profiles of nucleosomes bearing different epigenetic modifications on genome scale. We found that indels are depleted around nucleosome positions of all considered types, whereas single-nucleotide polymorphisms are enriched around the positions of bulk nucleosomes but depleted around the positions of epigenetically modified nucleosomes. These findings indicate an increased level of conservation for the sequences associated with epigenetically modified nucleosomes, highlighting complex organization of the human chromatin.

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  2. DOI: 10.1038/nsmb.2012
  3. View record in Web of Science®
  4. WOS: 000289195000019

Library Notes

  1. Fiscal Year: FY2010-2011
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