The Set1 N-terminal domain and Swd2 interact with RNA polymerase II CTD to recruit COMPASS

Nat Commun. 2020 May 1;11(1):2181. doi: 10.1038/s41467-020-16082-2.


Methylation of histone H3 lysine 4 (H3K4) by Set1/COMPASS occurs co-transcriptionally, and is important for gene regulation. Set1/COMPASS associates with the RNA polymerase II C-terminal domain (CTD) to establish proper levels and distribution of H3K4 methylations. However, details of CTD association remain unclear. Here we report that the Set1 N-terminal region and the COMPASS subunit Swd2, which interact with each other, are both needed for efficient CTD binding in Saccharomyces cerevisiae. Moreover, a single point mutation in Swd2 that affects its interaction with Set1 also impairs COMPASS recruitment to chromatin and H3K4 methylation. A CTD interaction domain (CID) from the protein Nrd1 can partially substitute for the Set1 N-terminal region to restore CTD interactions and histone methylation. However, even when Set1/COMPASS is recruited via the Nrd1 CID, histone H2B ubiquitylation is still required for efficient H3K4 methylation, indicating that H2Bub acts after the initial recruitment of COMPASS to chromatin.

Publication types

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

MeSH terms

  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation Sequencing
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / chemistry
  • Histones / metabolism
  • Lysine / metabolism
  • Methylation
  • Point Mutation
  • Protein Binding
  • Protein Domains
  • Protein Processing, Post-Translational
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Ubiquitination


  • Chromatin
  • Histones
  • NRD1 protein, S cerevisiae
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Histone-Lysine N-Methyltransferase
  • SET1 protein, S cerevisiae
  • SWD2 protein, S cerevisiae
  • RNA Polymerase II
  • RPB1 protein, S cerevisiae
  • Lysine