Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation Academic Article uri icon

Overview

MeSH Major

  • CREB-Binding Protein
  • Cell Cycle Proteins
  • Drosophila Proteins
  • Histones
  • Molecular Chaperones

abstract

  • The multifunctional Creb-binding protein (CBP) protein plays a pivotal role in many critical cellular processes. Here we demonstrate that the bromodomain of CBP binds to histone H3 acetylated on lysine 56 (K56Ac) with higher affinity than to its other monoacetylated binding partners. We show that autoacetylation of CBP is critical for the bromodomain-H3 K56Ac interaction, and we propose that this interaction occurs via autoacetylation-induced conformation changes in CBP. Unexpectedly, the bromodomain promotes acetylation of H3 K56 on free histones. The CBP bromodomain also interacts with the histone chaperone anti-silencing function 1 (ASF1) via a nearby but distinct interface. This interaction is necessary for ASF1 to promote acetylation of H3 K56 by CBP, indicating that the ASF1-bromodomain interaction physically delivers the histones to the histone acetyl transferase domain of CBP. A CBP bromodomain mutation manifested in Rubinstein-Taybi syndrome has compromised binding to both H3 K56Ac and ASF1, suggesting that these interactions are important for the normal function of CBP.

publication date

  • March 25, 2014

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3970516

Digital Object Identifier (DOI)

  • 10.1073/pnas.1319122111

PubMed ID

  • 24616510

Additional Document Info

start page

  • E1072

end page

  • 81

volume

  • 111

number

  • 12