Permanganate/S1 Nuclease Footprinting Reveals Non-B DNA Structures with Regulatory Potential across a Mammalian Genome

Cell Syst. 2017 Mar 22;4(3):344-356.e7. doi: 10.1016/j.cels.2017.01.013. Epub 2017 Feb 22.

Abstract

DNA in cells is predominantly B-form double helix. Though certain DNA sequences in vitro may fold into other structures, such as triplex, left-handed Z form, or quadruplex DNA, the stability and prevalence of these structures in vivo are not known. Here, using computational analysis of sequence motifs, RNA polymerase II binding data, and genome-wide potassium permanganate-dependent nuclease footprinting data, we map thousands of putative non-B DNA sites at high resolution in mouse B cells. Computational analysis associates these non-B DNAs with particular structures and indicates that they form at locations compatible with an involvement in gene regulation. Further analyses support the notion that non-B DNA structure formation influences the occupancy and positioning of nucleosomes in chromatin. These results suggest that non-B DNAs contribute to the control of a variety of critical cellular and organismal processes.

Keywords: DNA topology; H-DNA; SIDD; Z-DNA; chromatin; cruciform; non-B DNA; quadruplex; supercoiling; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chromatin
  • Computational Biology / methods
  • DNA / chemistry*
  • DNA / ultrastructure*
  • DNA Footprinting / methods*
  • DNA, Single-Stranded / ultrastructure
  • Fungal Proteins
  • G-Quadruplexes
  • Gene Expression Regulation / physiology
  • Genome
  • Mammals / genetics
  • Manganese Compounds / metabolism
  • Mice
  • Nucleic Acid Conformation
  • Nucleosomes
  • Oxides / metabolism
  • Protein Binding
  • Single-Strand Specific DNA and RNA Endonucleases

Substances

  • Chromatin
  • DNA, Single-Stranded
  • Fungal Proteins
  • Manganese Compounds
  • Nucleosomes
  • Oxides
  • permanganic acid
  • DNA
  • Endonuclease S1, Aspergillus
  • Single-Strand Specific DNA and RNA Endonucleases