A histone H3 methyltransferase controls DNA methylation in Neurospora crassa

Nature. 2001 Nov 15;414(6861):277-83. doi: 10.1038/35104508.


DNA methylation is involved in epigenetic processes such as X-chromosome inactivation, imprinting and silencing of transposons. We have demonstrated previously that dim-2 encodes a DNA methyltransferase that is responsible for all known cytosine methylation in Neurospora crassa. Here we report that another Neurospora gene, dim-5, is required for DNA methylation, as well as for normal growth and full fertility. We mapped dim-5 and identified it by transformation with a candidate gene. The mutant has a nonsense mutation in a SET domain of a gene related to histone methyltransferases that are involved in heterochromatin formation in other organisms. Transformation of a wild-type strain with a segment of dim-5 reactivated a silenced hph gene, apparently by 'quelling' of dim-5. We demonstrate that recombinant DIM-5 protein specifically methylates histone H3 and that replacement of lysine 9 in histone H3 with either a leucine or an arginine phenocopies the dim-5 mutation. We conclude that DNA methylation depends on histone methylation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromosomal Proteins, Non-Histone
  • Chromosome Mapping
  • Chromosomes, Fungal
  • Codon, Nonsense
  • DNA Methylation*
  • DNA, Fungal / metabolism*
  • Eukaryotic Cells / metabolism
  • Gene Expression Regulation, Fungal
  • Gene Silencing
  • Heterochromatin / metabolism
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase*
  • Histones / metabolism*
  • Lysine / metabolism
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism*
  • Molecular Sequence Data
  • Neurospora crassa / enzymology*
  • Neurospora crassa / genetics
  • Neurospora crassa / metabolism
  • Open Reading Frames
  • Protein Methyltransferases
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Sequence Alignment
  • Signal Transduction
  • Transcription Factors
  • Transgenes


  • Chromosomal Proteins, Non-Histone
  • Codon, Nonsense
  • DNA, Fungal
  • Heterochromatin
  • Histones
  • Proteins
  • Transcription Factors
  • Histone Methyltransferases
  • Methyltransferases
  • Protein Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Lysine