Formaldehyde-induced histone modifications in vitro

Chem Res Toxicol. 2008 Aug;21(8):1586-93. doi: 10.1021/tx8000576. Epub 2008 Jul 26.

Abstract

Numerous experiments have demonstrated the genotoxic and mutagenic effects of formaldehyde, including DNA-protein cross-links (DPC). Histone was reported to be involved in the formation of DPC in which the epsilon-amino groups of lysine and exocyclic amino groups of DNA were thought to be cross-linked through multiple step reactions. Using mass spectrometry, the N-terminus of histone and lysine residues located in both the histone N-terminal tail and the globular fold domain were identified as binding sites for formaldehyde in the current study. The observation that only lysine residues without post-translational modification (PTM) can be attacked by formaldehyde indicates that PTM blocks the reaction between lysine and formaldehyde. Additionally, we found that formaldehyde-induced Schiff bases on lysine residues could inhibit the formation of PTM on histone, raising the possibility that formaldehyde might alter epigenetic regulation.

Publication types

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

MeSH terms

  • Binding Sites
  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents / chemistry*
  • Cross-Linking Reagents / metabolism
  • DNA / drug effects
  • DNA Damage
  • Formaldehyde / chemistry*
  • Formaldehyde / metabolism
  • Histones / chemistry*
  • Histones / metabolism
  • In Vitro Techniques
  • Lysine / chemistry
  • Lysine / metabolism
  • Peptide Fragments / chemistry
  • Peptide Mapping
  • Protein Binding
  • Protein Structure, Tertiary
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry

Substances

  • Cross-Linking Reagents
  • Histones
  • Peptide Fragments
  • Formaldehyde
  • DNA
  • Lysine