LSD1: oxidative chemistry for multifaceted functions in chromatin regulation

Trends Biochem Sci. 2008 Apr;33(4):181-9. doi: 10.1016/j.tibs.2008.01.003. Epub 2008 Mar 17.


Three years after its discovery, lysine-specific demethylase 1 remains at the forefront of chromatin research. Its demethylase activity on Lys4 of histone H3 supports its role in gene repression. By contrast, the biochemical mechanisms underlying lysine-specific demethylase 1 involvement in transcriptional activation are not firmly established. Structural studies highlight a specific binding site for the histone H3 N-terminal tail and a catalytic machinery that is closely related to that of other flavin-dependent amine oxidases. These insights are crucial for the development of demethylation inhibitors. Furthermore, the exploration of putative non-histone substrates and potential signaling roles of hydrogen peroxide produced by the demethylation reaction could lead to new paradigms in chromatin biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Catalysis
  • Chromatin / metabolism*
  • Drug Design
  • Flavins / metabolism
  • Gene Expression Regulation
  • Histone Demethylases
  • Histones / chemistry*
  • Histones / metabolism
  • Humans
  • Hydrogen Peroxide / metabolism
  • Models, Biological
  • Oxidoreductases, N-Demethylating / metabolism
  • Oxidoreductases, N-Demethylating / physiology*
  • Oxygen / metabolism*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Signal Transduction


  • Chromatin
  • Flavins
  • Histones
  • Hydrogen Peroxide
  • Histone Demethylases
  • KDM1A protein, human
  • Oxidoreductases, N-Demethylating
  • Oxygen