Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Histone H3 K36 methylation is mediated by a trans-histone methylation pathway involving an interaction between Set2 and histone H4.

Set2-mediated H3 K36 methylation is an important histone modification on chromatin during transcription elongation. Although Set2 associates with the phosphorylated C-terminal domain (CTD) of RNA polymerase II (RNAPII), the mechanism of Set2 binding to chromatin and subsequent exertion of its methyltransferase activity is relatively uncharacterized. We identified a critical lysine residue in histone H4 that is needed for interaction with Set2 and proper H3 K36 di- and trimethylation. We also determined that the N terminus of Set2 contains a histone H4 interaction motif that allows Set2 to bind histone H4 and nucleosomes. A Set2 mutant lacking the histone H4 interaction motif is able to bind to the phosphorylated CTD of RNAPII and associate with gene-specific loci but is defective for H3 K36 di- and trimethylation. In addition, this Set2 mutant shows increased H4 acetylation and resistance to 6-Azauracil. Overall, our study defines a new interaction between Set2 and histone H4 that mediates trans-histone regulation of H3 K36 methylation, which is needed for the preventative maintenance and integrity of the genome.

Pubmed ID: 18923077


  • Du HN
  • Fingerman IM
  • Briggs SD


Genes & development

Publication Data

October 15, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM74183
  • Agency: NIGMS NIH HHS, Id: R01 GM074183
  • Agency: NIGMS NIH HHS, Id: R01 GM074183-01A1
  • Agency: NIGMS NIH HHS, Id: R01 GM074183-02
  • Agency: NIGMS NIH HHS, Id: R01 GM074183-03
  • Agency: NIGMS NIH HHS, Id: R01 GM074183-04

Mesh Terms

  • Antimetabolites
  • Blotting, Western
  • Chromatin
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation, Fungal
  • Histones
  • Immunoblotting
  • Immunoprecipitation
  • Lysine
  • Methylation
  • Methyltransferases
  • Mutation
  • Nucleosomes
  • Phosphorylation
  • Protein Kinases
  • Protein Processing, Post-Translational
  • RNA Polymerase II
  • Saccharomyces cerevisiae Proteins
  • Transcription, Genetic
  • Uracil