Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators

Mol Cell Biol. 2001 Jan;21(2):476-87. doi: 10.1128/MCB.21.2.476-487.2001.

Abstract

The transcriptional coactivator CREB binding protein (CBP) possesses intrinsic histone acetyltransferase (HAT) activity that is important for gene regulation. CBP binds to and cooperates with numerous nuclear factors to stimulate transcription, but it is unclear if these factors modulate CBP HAT activity. Our previous work showed that CBP interacts with the Epstein-Barr virus-encoded basic region zipper (b-zip) protein, Zta, and augments its transcriptional activity. Here we report that Zta strongly enhances CBP-mediated acetylation of nucleosomal histones. Zta stimulated the HAT activity of CBP that had been partially purified or immunoprecipitated from mammalian cells as well as from affinity-purified, baculovirus expressed CBP. Stimulation of nucleosome acetylation required the CBP HAT domain, the Zta DNA binding and transcription activation domain, and nucleosomal DNA. In addition to Zta, we found that two other b-zip proteins, NF-E2 and C/EBPalpha, strongly stimulated nucleosomal HAT activity. In contrast, several CBP-binding proteins, including phospho-CREB, JUN/FOS, GATA-1, Pit-1, and EKLF, failed to stimulate HAT activity. These results demonstrate that a subset of transcriptional activators enhance the nucleosome-directed HAT activity of CBP and suggest that nuclear factors may regulate transcription by altering substrate recognition and/or the enzymatic activity of chromatin modifying coactivators.

Publication types

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

MeSH terms

  • Acetylation
  • Acetyltransferases / chemistry
  • Acetyltransferases / metabolism*
  • Animals
  • Binding Sites
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • CREB-Binding Protein
  • Catalytic Domain
  • Cell Line
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Erythroid-Specific DNA-Binding Factors
  • G-Box Binding Factors
  • GATA1 Transcription Factor
  • Histone Acetyltransferases
  • Histones / metabolism
  • Humans
  • NF-E2 Transcription Factor
  • NF-E2 Transcription Factor, p45 Subunit
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism*
  • Nucleosomes / enzymology*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins*
  • Substrate Specificity
  • Trans-Activators / chemistry*
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection
  • Viral Proteins*

Substances

  • BZLF1 protein, Herpesvirus 4, Human
  • CCAAT-Enhancer-Binding Protein-alpha
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • G-Box Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Histones
  • NF-E2 Transcription Factor
  • NF-E2 Transcription Factor, p45 Subunit
  • NFE2 protein, human
  • Nuclear Proteins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Viral Proteins
  • DNA
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases