Structure of the p300 catalytic core and implications for chromatin targeting and HAT regulation

Nat Struct Mol Biol. 2013 Sep;20(9):1040-6. doi: 10.1038/nsmb.2642. Epub 2013 Aug 11.


CBP and p300 are histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. Mutations in their catalytic 'cores' are linked to genetic disorders, including cancer. Here we present the 2.8-Å crystal structure of the catalytic core of human p300 containing its bromodomain, CH2 region and HAT domain. The structure reveals that the CH2 region contains a discontinuous PHD domain interrupted by a RING domain. The bromodomain, PHD, RING and HAT domains adopt an assembled configuration with the RING domain positioned over the HAT substrate-binding pocket. Disease mutations that disrupt RING attachment led to upregulation of HAT activity, thus revealing an inhibitory role for this domain. The structure provides a starting point for understanding how chromatin-substrate targeting and HAT regulation are coupled and why mutations in the p300 core lead to dysregulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain / genetics
  • Cell Line
  • Chromatin / metabolism*
  • Crystallography, X-Ray
  • Enzyme Stability
  • Humans
  • Models, Molecular
  • Mutation
  • Protein Interaction Domains and Motifs
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity
  • p300-CBP Transcription Factors / chemistry*
  • p300-CBP Transcription Factors / genetics
  • p300-CBP Transcription Factors / metabolism*


  • Chromatin
  • Recombinant Fusion Proteins
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor

Associated data

  • PDB/4BHW