Coordination of a transcriptional switch by HMGI(Y) acetylation

Science. 2001 Aug 10;293(5532):1133-6. doi: 10.1126/science.293.5532.1133.

Abstract

Dynamic control of interferon-beta (IFN-beta) gene expression requires the regulated assembly and disassembly of the enhanceosome, a higher-order nucleoprotein complex formed in response to virus infection. The enhanceosome activates transcription by recruiting the histone acetyltransferase proteins CREB binding protein (CBP) and p300/CBP-associated factors (PCAF)/GCN5, which, in addition to modifying histones, acetylate HMGI(Y), the architectural component required for enhanceosome assembly. We show that the accurate execution of the IFN-beta transcriptional switch depends on the ordered acetylation of the high-mobility group I protein HMGI(Y) by PCAF/GCN5 and CBP, which acetylate HMGI(Y) at distinct lysine residues on endogenous promoters. Whereas acetylation of HMGI(Y) by CBP at lysine-65 destabilizes the enhanceosome, acetylation of HMGI(Y) by PCAF/GCN5 at lysine-71 potentiates transcription by stabilizing the enhanceosome and preventing acetylation by CBP.

Publication types

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

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism
  • Amino Acid Sequence
  • CREB-Binding Protein
  • Cell Cycle Proteins
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation*
  • HMGA1a Protein
  • HeLa Cells
  • High Mobility Group Proteins / chemistry
  • High Mobility Group Proteins / metabolism*
  • Histone Acetyltransferases
  • Histones / metabolism
  • Humans
  • Interferon-beta / genetics*
  • Lysine / metabolism
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Recombinant Proteins / metabolism
  • Respirovirus / physiology
  • Saccharomyces cerevisiae Proteins*
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Transfection
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • High Mobility Group Proteins
  • Histones
  • Nuclear Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • HMGA1a Protein
  • Interferon-beta
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases
  • KAT2A protein, human
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Lysine