Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation

Mol Cell. 2000 Jun;5(6):905-15. doi: 10.1016/s1097-2765(00)80256-7.

Abstract

Histone acetylation and phosphorylation have separately been suggested to affect chromatin structure and gene expression. Here we report that these two modifications are synergistic. Stimulation of mammalian cells by epidermal growth factor (EGF) results in rapid and sequential phosphorylation and acetylation of H3, and these dimodified H3 molecules are preferentially associated with the EGF-activated c-fos promoter in a MAP kinase-dependent manner. In addition, the prototypical histone acetyltransferase Gcn5 displays an up to 10-fold preference for phosphorylated (Ser-10) H3 over nonphosphorylated H3 as substrate in vitro, suggesting that H3 phosphorylation can affect the efficiency of subsequent acetylation reactions. Together, these results illustrate how the addition of multiple histone modifications may be coupled during the process of gene expression.

Publication types

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

MeSH terms

  • Acetylation / drug effects
  • Acetyltransferases / chemistry
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA-Binding Proteins*
  • Epidermal Growth Factor / pharmacology*
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Genes, fos / genetics
  • Histone Acetyltransferases
  • Histones / chemistry
  • Histones / immunology
  • Histones / metabolism*
  • Kinetics
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Inbred C3H
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / genetics
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Substrate Specificity

Substances

  • Antibodies
  • Chromatin
  • DNA-Binding Proteins
  • Fungal Proteins
  • Histones
  • Saccharomyces cerevisiae Proteins
  • Epidermal Growth Factor
  • Acetyltransferases
  • GCN5 protein, S cerevisiae
  • Histone Acetyltransferases
  • Protein Kinases
  • Mitogen-Activated Protein Kinases