Cited by 169Epigenetics and DNA MethylationGenomics and Chromatin DynamicsDNA and Nucleic Acid Chemistry

Probing DNA shape and methylation state on a genomic scale with DNase I

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Lazarovici, Allan, Zhou, Tianyin, Shafer, Anthony, Dantas Machado, Ana Carolina, Riley, Todd R., Sandstrom, Richard, Sabo, Peter J., Lu, Yan +3 more·2013·Proceedings of the National Academy of Sciences

Abstract

DNA binding proteins find their cognate sequences within genomic DNA through recognition of specific chemical and structural features. Here we demonstrate that high-resolution DNase I cleavage profiles can provide detailed information about the shape and chemical modification status of genomic DNA. Analyzing millions of DNA backbone hydrolysis events on naked genomic DNA, we show that the intrinsic rate of cleavage by DNase I closely tracks the width of the minor groove. Integration of these DNase I cleavage data with bisulfite sequencing data for the same cell type’s genome reveals that cleavage directly adjacent to cytosine-phosphate-guanine (CpG) dinucleotides is enhanced at least eightfold by cytosine methylation. This phenomenon we show to be attributable to methylation-induced narrowing of the minor groove. Furthermore, we demonstrate that it enables simultaneous mapping of DNase I hypersensitivity and regional DNA methylation levels using dense in vivo cleavage data. Taken together, our results suggest a general mechanism by which CpG methylation can modulate protein–DNA interaction strength via the remodeling of DNA shape.

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Crossref · 10.1073/pnas.1216822110

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  • Adding a methyl group to cytosine can affect local DNA shape, as shown by altered DNase I digestion rate and patterns.

    “Adding a methyl group to the cytosine could affect the local DNA shape, as evidenced by the altered DNase I digestion rate and patterns70,71.”

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Authors
Lazarovici, A., Zhou, T., Shafer, A., Dantas Machado, A. C., Riley, T. R., Sandstrom, R., Sabo, P. J., Lu, Y., Rohs, R., Stamatoyannopoulos, J. A., & Bussemaker, H. J.
Affiliations
  • Columbia University (US)
  • University of Southern California (US)
  • University of Washington (US)
  • Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics and Astronomy, and Computer Science, University of Southern California, Los Angeles, CA 90089;
Venue
Proceedings of the National Academy of Sciences
Published
2013-04
Volume
110
Issue
16
Pages
6376-6381
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1984521378
Cited by
162
References
47
Citations by year
2026: 6 · 2025: 5 · 2024: 9 · 2023: 4 · 2022: 14 · 2021: 15 · 2020: 11 · 2019: 19 · 2018: 12 · 2017: 17 · 2016: 13 · 2015: 19 · 2014: 12 · 2013: 6
FWCI
7.47
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Human Genome Research Institute (U54HG004592, R01HG003008)
  • National Cancer Institute (U54CA121852)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
DNase I cleavage, DNA methylation, CpG, DNA shape, DNase I hypersensitivity, bisulfite sequencing, protein-DNA interactions
MeSH terms
Cells, Cultured, Deoxyribonuclease I, DNA, Humans, Models, Genetic, Models, Molecular, Nucleic Acid Conformation, Sequence Analysis, DNA, CpG Islands, DNA Methylation, Genomics

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