Covalent Modifications of Histone H3K9 Promote Binding of CHD3
Adam H. Tencer,
Khan L. Cox,
Luo Di,
Joseph B. Bridgers,
Jie Lyu,
Xiaodong Wang,
Jennifer K. Sims,
Tyler M. Weaver,
Hillary F. Allen,
Yi Zhang,
Jovylyn Gatchalian,
Michael A. Darcy,
Matthew D. Gibson,
Jinzen Ikebe,
Wei Li,
Paul A. Wade,
Jeffrey J. Hayes,
Brian D. Strahl,
Hidetoshi Kono,
Michael G. Poirier,
Catherine A. Musselman,
Tatiana G. Kutateladze
Affiliations
Adam H. Tencer
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Khan L. Cox
Department of Physics, Ohio State University, Columbus, OH 43210, USA
Luo Di
Molecular Modeling and Simulation Group, National Institutes for Quantum and Radiological Science and Technology, Kizugawa, Kyoto 619 0215, Japan
Joseph B. Bridgers
Department of Biochemistry and Biophysics and the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Jie Lyu
Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Xiaodong Wang
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
Jennifer K. Sims
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Tyler M. Weaver
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242, USA
Hillary F. Allen
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Yi Zhang
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Jovylyn Gatchalian
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Michael A. Darcy
Department of Physics, Ohio State University, Columbus, OH 43210, USA
Matthew D. Gibson
Department of Physics, Ohio State University, Columbus, OH 43210, USA
Jinzen Ikebe
Molecular Modeling and Simulation Group, National Institutes for Quantum and Radiological Science and Technology, Kizugawa, Kyoto 619 0215, Japan
Wei Li
Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Paul A. Wade
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Jeffrey J. Hayes
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, NY 14642, USA
Brian D. Strahl
Department of Biochemistry and Biophysics and the Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Hidetoshi Kono
Molecular Modeling and Simulation Group, National Institutes for Quantum and Radiological Science and Technology, Kizugawa, Kyoto 619 0215, Japan
Michael G. Poirier
Department of Physics, Ohio State University, Columbus, OH 43210, USA; Corresponding author
Catherine A. Musselman
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242, USA; Corresponding author
Tatiana G. Kutateladze
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Corresponding author
Summary: Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3) whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9—methylation or acetylation (H3K9me3 or H3K9ac)—enhance this interaction. Binding of CHD3 PHDs promotes H3K9Cme3-nucleosome unwrapping in vitro and perturbs the pericentric heterochromatin structure in vivo. Methylation or acetylation of H3K9 uniquely alleviates the intra-nucleosomal interaction of histone H3 tails, increasing H3K9 accessibility. Collectively, our data suggest that the targeting of covalently modified H3K9 by CHD3 might be essential in diverse functions of NuRD. : Tencer et al. find that CHD3 co-localizes with the other subunits of the NuRD complex and H3K9ac at NuRD target genes. The authors further demonstrate that the PHD fingers of CHD3 associate with histone H3 tails, and this association is augmented through methylation or acetylation of H3K9. Keywords: CHD3, NuRD, PHD finger, H3K9me3, H3K9ac, histone, chromatin
