Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS

Mol Cell Biol. 2008 Dec;28(24):7337-44. doi: 10.1128/MCB.00976-08. Epub 2008 Oct 6.


In yeast, the macromolecular complex Set1/COMPASS is capable of methylating H3K4, a posttranslational modification associated with actively transcribed genes. There is only one Set1 in yeast; yet in mammalian cells there are multiple H3K4 methylases, including Set1A/B, forming human COMPASS complexes, and MLL1-4, forming human COMPASS-like complexes. We have shown that Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes. RNA interference-mediated knockdown of Wdr82 results in a reduction in the H3K4 trimethylation levels, although these cells still possess active MLL complexes. Comprehensive in vitro enzymatic studies with Set1 and MLL complexes demonstrated that the Set1 complex is a more robust H3K4 trimethylase in vitro than the MLL complexes. Given our in vivo and in vitro observations, it appears that the human Set1 complex plays a more widespread role in H3K4 trimethylation than do the MLL complexes in mammalian cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Macromolecular Substances / metabolism*
  • Methylation
  • Protein Methyltransferases / genetics
  • Protein Methyltransferases / metabolism*
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism


  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histones
  • Macromolecular Substances
  • Protein Subunits
  • RNA, Small Interfering
  • WDR82 protein, human
  • Histone Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Setd1A protein, human
  • Lysine