title: Analysis of the Histone H3.1 Interactome: A Suitable Chaperone for the Right Event.
abstract: Despite minimal disparity at the sequence level, mammalian H3 variants bind to distinct sets of polypeptides. Although histone H3.1 predominates in cycling cells, our knowledge of the soluble complexes that it forms en route to deposition or following eviction from chromatin remains limited. Here, we provide a comprehensive analysis of the H3.1-binding proteome, with emphasis on its interactions with histone chaperones and components of the replication fork. Quantitative mass spectrometry revealed 170 protein interactions, whereas a large-scale biochemical fractionation of H3.1 and associated enzymatic activities uncovered over twenty stable protein complexes in dividing human cells. The sNASP and ASF1 chaperones play pivotal roles in the processing of soluble histones but do not associate with the active CDC45/MCM2-7/GINS (CMG) replicative helicase. We also find TONSL-MMS22L to function as a H3-H4 histone chaperone. It associates with the regulatory MCM5 subunit of the replicative helicase.
authors.affiliation: Howard Hughes Medical Institute, New York University School of Medicine, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, NY 10016, USA.
authors.forename: Eric I
authors.initials: EI
authors.lastname: Campos
authors.affiliation: Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands 6525 GA.
authors.forename: Arne H
authors.initials: AH
authors.lastname: Smits
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, NY 10021, USA.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kang
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Department of Molecular Genetics, University of Toronto, Toronto M5G 1X5, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Landry
authors.affiliation: Howard Hughes Medical Institute, New York University School of Medicine, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, NY 10016, USA.
authors.forename: Thelma M
authors.initials: TM
authors.lastname: Escobar
authors.affiliation: Office of Collaborative Science, New York University School of Medicine, NY 10016, USA.
authors.forename: Shruti
authors.initials: S
authors.lastname: Nayak
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, NY 10016, USA.
authors.forename: Beatrix M
authors.initials: BM
authors.lastname: Ueberheide
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Department of Molecular Genetics, University of Toronto, Toronto M5G 1X5, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Durocher
authors.affiliation: Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands 6525 GA.
authors.forename: Michiel
authors.initials: M
authors.lastname: Vermeulen
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, NY 10021, USA.
authors.forename: Jerard
authors.initials: J
authors.lastname: Hurwitz
authors.affiliation: Howard Hughes Medical Institute, New York University School of Medicine, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, NY 10016, USA. Electronic address: danny.reinberg@nyumc.org.
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006657:Histones; C489423:MCM5 protein, human; C554517:MMS22L protein, human; D016328:NF-kappa B; D009687:Nuclear Proteins; C093394:TONSL protein, human; D064110:Minichromosome Maintenance Proteins