Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity

Biochem Biophys Res Commun. 2006 Jun 23;345(1):318-23. doi: 10.1016/j.bbrc.2006.04.095. Epub 2006 Apr 27.


Evolutionary conserved SET domains were originally identified in three Drosophila proteins: suppressor of variegation (Su (var) 3-9), enhancer of zeste (E(z)), and the trithorax. Some of the SET-domain containing proteins have been known to elicit methylation of histone lysine residues. Based on a search for SET-domain containing proteins using bioinformatic tools, we identified and subsequently named a novel SET domain as WHISTLE, that has histone methyltransferase (HMTase) activity. To characterize WHISTLE, we performed an HMTase assay, mass spectrometric analysis, lysine specificity, and transfection assays. Mass spectrometric and immunoblot analysis revealed that WHISTLE di-methylates H3K4 and di-, and tri-methylates H3K27 of histones. Overexpression of WHISTLE repressed transcription of the SV40 promoter. Our results suggest that WHISTLE is a novel SET domain containing a protein with specific H3K4 and H3K27 HMTase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bone Marrow Cells / metabolism*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins
  • Enzyme Activation
  • Histone Chaperones
  • Histone-Lysine N-Methyltransferase
  • Histones / chemistry
  • Histones / metabolism*
  • Humans
  • Methyltransferases / chemistry
  • Methyltransferases / metabolism*
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Repressor Proteins / chemistry*
  • Repressor Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*


  • Carrier Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histone Chaperones
  • Histones
  • Repressor Proteins
  • SET protein, human
  • Transcription Factors
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • NSD2 protein, human