Interaction of histone acetylases and deacetylases in vivo

Mol Cell Biol. 2003 Feb;23(3):1025-33. doi: 10.1128/MCB.23.3.1025-1033.2003.

Abstract

Having opposing enzymatic activities, histone acetylases (HATs) and deacetylases affect chromatin and regulate transcription. The activities of the two enzymes are thought to be balanced in the cell by an unknown mechanism that may involve their direct interaction. Using fluorescence resonance energy transfer analysis, we demonstrated that the acetylase PCAF and histone deacetylase 1 (HDAC1) are in close spatial proximity in living cells, compatible with their physical interaction. In agreement, coimmunoprecipitation assays demonstrated that endogenous HDACs are associated with PCAF and another acetylase, GCN5, in HeLa cells. We found by glycerol gradient sedimentation analysis that HATs are integrated into a large multiprotein HDAC complex that is distinct from the previously described HDAC complexes containing mSin3A, Mi-2/NRD, or CoREST. This HDAC-HAT association is partly accounted for by a direct protein-protein interaction observed in vitro. The HDAC-HAT complex may play a role in establishing a dynamic equilibrium of the two enzymes in vivo.

MeSH terms

  • Acetyltransferases / chemistry
  • Acetyltransferases / metabolism*
  • Cell Cycle Proteins
  • Cell Differentiation
  • Fluorescence Resonance Energy Transfer
  • HeLa Cells
  • Histone Acetyltransferases
  • Histone Deacetylase 1
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / metabolism*
  • Humans
  • In Vitro Techniques
  • Macromolecular Substances
  • Multiprotein Complexes
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism
  • Transcription Factors
  • U937 Cells
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Macromolecular Substances
  • Multiprotein Complexes
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Acetyltransferases
  • Histone Acetyltransferases
  • KAT2A protein, human
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • HDAC1 protein, human
  • Histone Deacetylase 1
  • Histone Deacetylases