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A viral mechanism for inhibition of p300 and PCAF acetyltransferase activity

D Chakravarti1, V Ogryzko, H Y Kao

  • 1Gene Expression Laboratory, The Salk Institute for Biological Sciences, La Jolla, California 92037, USA.

Cell
|February 20, 1999
PubMed

Insights

Adenoviral E1A oncoprotein inhibits histone acetyltransferases (HATs) p300/CBP and PCAF, key regulators of gene transcription. This repression of HAT activity by E1A offers a new understanding of transcriptional regulation.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Virology

Background:

  • Nucleosomal histone modification is crucial for RNA polymerase II-dependent transcription.
  • Histone acetyltransferases (HATs) like p300/CBP and PCAF act as coactivators for transcription factors, promoting histone acetylation and forming activation complexes.
  • Adenoviral E1A oncoprotein is known to repress transcriptional signaling by interacting with p300/CBP and displacing other proteins.

Purpose of the Study:

  • To investigate the direct effect of adenoviral E1A oncoprotein on the activity of p300/CBP and PCAF histone acetyltransferases.
  • To determine if E1A modulates histone acetylation and transcription in vivo.
  • To elucidate the mechanism by which E1A represses transcription.

Main Methods:

  • In vitro assays to measure the HAT activity of p300/CBP and PCAF in the presence of E1A.
  • In vivo studies to assess p300-dependent transcription.
  • Analysis of nucleosomal histone modifications and p53 acetylation.

Main Results:

  • E1A directly represses the histone acetyltransferase (HAT) activity of both p300/CBP and PCAF in vitro.
  • E1A inhibits p300-dependent transcription in vivo.
  • E1A blocks nucleosomal histone modifications mediated by the PCAF complex and inhibits p53 acetylation.

Conclusions:

  • Adenoviral E1A oncoprotein directly inhibits the enzymatic activity of key histone acetyltransferases (HATs).
  • E1A-mediated repression of HAT activity represents a novel mechanism for regulating transcription.
  • These findings provide insights into viral oncoprotein function and epigenetic regulation of gene expression.

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