DCAF26, an adaptor protein of Cul4-based E3, is essential for DNA methylation in Neurospora crassa

PLoS Genet. 2010 Sep 23;6(9):e1001132. doi: 10.1371/journal.pgen.1001132.


DNA methylation is involved in gene silencing and genome stability in organisms from fungi to mammals. Genetic studies in Neurospora crassa previously showed that the CUL4-DDB1 E3 ubiquitin ligase regulates DNA methylation via histone H3K9 trimethylation. However, the substrate-specific adaptors of this ligase that are involved in the process were not known. Here, we show that, among the 16 DDB1- and Cul4-associated factors (DCAFs) encoded in the N. crassa genome, three interacted strongly with CUL4-DDB1 complexes. DNA methylation analyses of dcaf knockout mutants revealed that dcaf26 was required for all of the DNA methylation that we observed. In addition, histone H3K9 trimethylation was also eliminated in dcaf26(KO) mutants. Based on the finding that DCAF26 associates with DDB1 and the histone methyltransferase DIM-5, we propose that DCAF26 protein is the major adaptor subunit of the Cul4-DDB1-DCAF26 complex, which recruits DIM-5 to DNA regions to initiate H3K9 trimethylation and DNA methylation in N. crassa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / isolation & purification
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Cullin Proteins / metabolism*
  • DNA Methylation*
  • DNA, Fungal / metabolism
  • Fungal Proteins / chemistry
  • Fungal Proteins / isolation & purification
  • Fungal Proteins / metabolism*
  • Gene Knockout Techniques
  • Genes, Fungal / genetics
  • Histones / metabolism
  • Lysine / metabolism
  • Molecular Sequence Data
  • Neurospora crassa / cytology
  • Neurospora crassa / enzymology
  • Neurospora crassa / genetics
  • Neurospora crassa / metabolism*
  • Protein Binding
  • Sequence Alignment
  • Ubiquitin-Protein Ligases / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Cullin Proteins
  • DNA, Fungal
  • Fungal Proteins
  • Histones
  • Ubiquitin-Protein Ligases
  • Lysine