Drosophila Set1 is the major histone H3 lysine 4 trimethyltransferase with role in transcription

EMBO J. 2011 Jun 21;30(14):2817-28. doi: 10.1038/emboj.2011.194.


Histone H3 lysine 4 trimethylation (H3K4me3) is a major hallmark of promoter-proximal histones at transcribed genes. Here, we report that a previously uncharacterized Drosophila H3K4 methyltransferase, dSet1, and not the other putative histone H3K4 methyltransferases (Trithorax; Trithorax-related protein), is predominantly responsible for histone H3K4 trimethylation. Functional and proteomics studies reveal that dSet1 is a component of a conserved H3K4 trimethyltransferase complex and polytene staining and live cell imaging assays show widespread association of dSet1 with transcriptionally active genes. dSet1 is present at the promoter region of all tested genes, including activated Hsp70 and Hsp26 heat shock genes and is required for optimal mRNA accumulation from the tested genes. In the case of Hsp70, the mRNA production defect in dSet1 RNAi-treated cells is accompanied by retention of Pol II at promoters. Our data suggest that dSet1-dependent H3K4me3 is responsible for the generation of a chromatin structure at active promoters that ensures optimal Pol II release into productive elongation.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / genetics*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Histones / metabolism
  • Immunoprecipitation
  • Lysine
  • Methylation
  • Promoter Regions, Genetic / genetics*
  • RNA Polymerase II / genetics*
  • RNA Polymerase II / metabolism
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*


  • Drosophila Proteins
  • Heat-Shock Proteins
  • Histones
  • RNA, Messenger
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • RNA Polymerase II
  • Lysine