Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin

Mol Cell. 2003 Nov;12(5):1325-32. doi: 10.1016/s1097-2765(03)00438-6.

Abstract

Set1p methylates lysine 4 (K4) of histone H3 and regulates the expression of many genes in yeast. Here we use a biochemical approach to identify a protein, Isw1p, which recognizes chromatin preferentially when it is di- and trimethylated at K4 H3. We show that on certain actively transcribed genes, the Isw1p chromatin remodeling ATPase requires K4 H3 methylation to associate with chromatin in vivo. Analysis of one such gene, MET16, shows that the enzymatic activities of Set1p and Isw1p are functionally connected: Set1p methylation and Isw1p ATPase generate specific chromatin changes at the 5' end of the gene, are necessary for the correct distribution of RNA polymerase II over the coding region, and are required for the recruitment of the cleavage and polyadenylation factor Rna15p. These results indicate that K4 H3 methylation and Isw1p ATPase activity are intimately linked in regulating transcription of certain genes in yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Chromatin / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Histones / chemistry*
  • Histones / metabolism*
  • Humans
  • Lysine / metabolism*
  • Methionine / metabolism
  • Methylation
  • Protein Binding
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histones
  • Saccharomyces cerevisiae Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • Methionine
  • RNA Polymerase II
  • Adenosine Triphosphatases
  • ISW1 protein, S cerevisiae
  • SMARCA5 protein, human
  • Lysine