title: Binding of the histone chaperone ASF1 to the CBP bromodomain promotes histone acetylation.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Chandrima
authors.initials: C
authors.lastname: Das
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Roy
authors.forename: Sarita
authors.initials: S
authors.lastname: Namjoshi
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Malarkey
authors.forename: David N M
authors.initials: DN
authors.lastname: Jones
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
authors.forename: Mair E A
authors.initials: ME
authors.lastname: Churchill
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Tyler
mesh_terms: D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D050882:CREB-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D006657:Histones; D018832:Molecular Chaperones; C491642:asf1 protein, Drosophila; D050882:CREB-Binding Protein