Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 12, Pages E1072-E1081Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1319122111
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Funding
- University of Colorado Cancer Center Support Grant [P30CA046934]
- NIH [GM64475]
- Cancer Prevention and Research Institute of Texas Rising Star
- University of Texas Texas Stars and Senior Trust Recruitment Awards
- National Institutes of Health [R01GM079154, RO1GM096863]
- Susan Komen Race for the Cure Fellowship
- Department of Biotechnology, Ministry of Science and Technology, Government of India
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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.
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