CLLD8/KMT1F is a lysine methyltransferase that is important for chromosome segregation

J Biol Chem. 2010 Jun 25;285(26):20234-41. doi: 10.1074/jbc.M109.052399. Epub 2010 Apr 19.

Abstract

Proteins bearing a SET domain have been shown to methylate lysine residues in histones and contribute to chromatin architecture. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression. Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Consistently, depletion in CLLD8/KMT1F coincides with a loss of CENP proteins and delayed mitosis, suggesting that this protein participates in chromosome condensation and segregation. Altogether, our results provide evidence that CLLD8/KMT1F is recruited to heterochromatin regions and contributes in vivo to the deposition of trimethyl marks in concert with SUV39H1/KMT1A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Chromosome Segregation*
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HeLa Cells
  • Heterochromatin / metabolism
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Indoles / chemistry
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Microscopy, Confocal
  • Mitosis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • Heterochromatin
  • Histones
  • Indoles
  • Nuclear Proteins
  • Repressor Proteins
  • Green Fluorescent Proteins
  • DAPI
  • SUV39H1 protein, human
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase