2. Academic Validation
  3. Analysis of the Histone H3.1 Interactome: A Suitable Chaperone for the Right Event

Analysis of the Histone H3.1 Interactome: A Suitable Chaperone for the Right Event

  • Mol Cell. 2015 Nov 19;60(4):697-709. doi: 10.1016/j.molcel.2015.08.005.
Eric I Campos 1,  Arne H Smits 2,  Young-Hoon Kang 3,  Sébastien Landry 4,  Thelma M Escobar 1,  Shruti Nayak 5,  Beatrix M Ueberheide 6,  Daniel Durocher 4,  Michiel Vermeulen 2,  Jerard Hurwitz 3,  Danny Reinberg 7
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands 6525 GA.
  • 3 Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, NY 10021, USA.
  • 4 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and Department of Molecular Genetics, University of Toronto, Toronto M5G 1X5, Canada.
  • 5 Office of Collaborative Science, New York University School of Medicine, NY 10016, USA.
  • 6 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, NY 10016, USA.
  • 7 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.
PMID: 26527279 DOI: 10.1016/j.molcel.2015.08.005
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.

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