A non-canonical monovalent zinc finger stabilizes the integration of Cfp1 into the H3K4 methyltransferase complex COMPASS

Nucleic Acids Res. 2020 Jan 10;48(1):421-431. doi: 10.1093/nar/gkz1037.


COMPlex ASsociating with SET1 (COMPASS) is a histone H3 Lys-4 methyltransferase that typically marks the promoter region of actively transcribed genes. COMPASS is a multi-subunit complex in which the catalytic unit, SET1, is required for H3K4 methylation. An important subunit known to regulate SET1 methyltransferase activity is the CxxC zinc finger protein 1 (Cfp1). Cfp1 binds to COMPASS and is critical to maintain high level of H3K4me3 in cells but the mechanisms underlying its stimulatory activity is poorly understood. In this study, we show that Cfp1 only modestly activates COMPASS methyltransferase activity in vitro. Binding of Cfp1 to COMPASS is in part mediated by a new type of monovalent zinc finger (ZnF). This ZnF interacts with the COMPASS's subunits RbBP5 and disruption of this interaction blunts its methyltransferase activity in cells and in vivo. Collectively, our studies reveal that a novel form of ZnF on Cfp1 enables its integration into COMPASS and contributes to epigenetic signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Chaetomium / genetics
  • Chaetomium / metabolism
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Epigenesis, Genetic
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Fungal Proteins / chemistry*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Histone-Lysine N-Methyltransferase / chemistry*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / chemistry*
  • Histones / genetics
  • Histones / metabolism
  • Kinetics
  • Methylation
  • Models, Molecular
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc / metabolism
  • Zinc Fingers*


  • Fungal Proteins
  • Histones
  • Recombinant Proteins
  • Transcription Factors
  • histone H3 trimethyl Lys4
  • Histone-Lysine N-Methyltransferase
  • Zinc