The cysteine-rich domain of TET2 binds preferentially to mono- and dimethylated histone H3K36

J Biochem. 2017 Apr 1;161(4):327-330. doi: 10.1093/jb/mvx004.

Abstract

Missense mutations in Ten-eleven translocation 2 (TET2) gene are frequently found in leukaemia patients. Although mutations span the entire coding region, they tend to cluster in the C-terminal enzymatic domain and a cysteine-rich (CR) domain of unknown function. Herein, we found the CR domain binds chromatin preferentially at the histone H3 tail by recognising H3 lysine 36 mono- and dimethylation (H3K36me1/2). Importantly, missense mutations in the CR domain perturbed TET2 recruitment to the target locus and its enzymatic activities. Our findings identify a novel H3K36me recognition domain and uncover a critical link between histone modification and DNA hydroxylation in leukaemogenesis.

Keywords: TET2; epigenetics; histone H3K36 methylation; histones < chromosomes; leukaemia.

MeSH terms

  • Binding Sites / genetics
  • Chromatin / metabolism
  • Cysteine / genetics
  • Cysteine / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dioxygenases
  • HEK293 Cells
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Immunoblotting
  • Lysine / chemistry
  • Lysine / metabolism*
  • Methylation
  • Microscopy, Confocal
  • Models, Molecular
  • Mutation, Missense
  • Protein Binding
  • Protein Domains
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • Proto-Oncogene Proteins
  • Dioxygenases
  • TET2 protein, human
  • Lysine
  • Cysteine