Genetically directing ɛ-N, N-dimethyl-L-lysine in recombinant histones

Chem Biol. 2010 Oct 29;17(10):1072-6. doi: 10.1016/j.chembiol.2010.07.013.


A molecular understanding of the biological phenomena orchestrated by lysine N(ɛ)-methylation is impeded by the challenge of producing site-specifically and quantitatively methylated histones. Here, we report a general method that combines genetic code expansion and chemoselective reactions, for the quantitative, site-specific installation of dimethyl-lysine in recombinant histones. We demonstrate the utility of our method by preparing H3K9me2 and show that this modified histone is specifically recognized by heterochromatin protein 1 beta. Extensions of the strategy reported here will allow a range of chemoselective reactions (which have been used for residue-selective, but not site-selective protein modification) to be leveraged for site-specific protein modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / metabolism
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Immunoprecipitation
  • Lysine / metabolism*
  • Methylation
  • Protein Processing, Post-Translational
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Chromosomal Proteins, Non-Histone
  • Histones
  • Recombinant Proteins
  • Chromobox Protein Homolog 5
  • Lysine