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Nat Struct Mol Biol. 2011 Apr;18(4):510-5. doi: 10.1038/nsmb.2012. Epub 2011 Mar 13.

Impact of chromatin structure on sequence variability in the human genome.

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1
Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA.

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.

PMID:
21399641
PMCID:
PMC3188321
DOI:
10.1038/nsmb.2012
[Indexed for MEDLINE]
Free PMC Article
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