Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein

Cell. 2001 Jan 12;104(1):119-30. doi: 10.1016/s0092-8674(01)00196-9.

Abstract

Acetylation of histones by p300/CBP and PCAF is considered to be a critical step in transcriptional regulation. In order to understand the role of cellular activities that modulate histone acetylation and transcription, we have purified and characterized a multiprotein cellular complex that potently inhibits the histone acetyltransferase activity of p300/CBP and PCAF. We have mapped a novel acetyltransferase-inhibitory domain of this INHAT (inhibitor of acetyltransferases) complex that binds to histones and masks them from being acetyltransferase substrates. Endogenous INHAT subunits, which include the Set/TAF-Ibeta oncoprotein, associate with chromatin in vivo and can block coactivatormediated transcription when transfected in cells. We propose that histone masking by INHAT plays a regulatory role in chromatin modification and serves as a novel mechanism of transcriptional regulation.

Publication types

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

MeSH terms

  • Acetylation
  • Acetyltransferases / chemistry
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Mapping
  • HeLa Cells
  • Histone Acetyltransferases
  • Histone Chaperones
  • Histones / genetics*
  • Histones / metabolism*
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Binding / genetics
  • Protein Structure, Tertiary
  • Proteins / genetics
  • Proteins / metabolism
  • Receptors, Retinoic Acid / physiology
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction / physiology
  • Transcription Factors*
  • Transcription, Genetic / physiology
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Histone Chaperones
  • Histones
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • Receptors, Retinoic Acid
  • SET protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Acetyltransferases
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor