DNA-mediated association of two histone-bound CAF-1 complexes drives tetrasome assembly in the wake of DNA replication
- Howard Hughes Medical Institute, University of Colorado, Boulder, United States
- Weill Cornell Graduate School of Medical Sciences, United States
- University of Colorado, Boulder, United States
- Memorial Sloan Kettering Cancer Center, United States
- Colorado State University, United States
Abstract
Nucleosome assembly in the wake of DNA replication is a key process that regulates cell identity and survival. Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with the replisome and orchestrates chromatin assembly following DNA synthesis. Little is known about the mechanism and structure of this key complex. Here we investigate the CAF-1•H3-H4 binding mode and the mechanism of nucleosome assembly. We show that CAF-1 binding to a H3-H4 dimer activates the Cac1 winged helix domain interaction with DNA. This drives the formation of a transient CAF-1•histone•DNA intermediate containing two CAF-1 complexes, each associated with one H3-H4 dimer. Here, the (H3-H4)2 tetramer is formed and deposited onto DNA. Our work elucidates the molecular mechanism for histone deposition by CAF-1, a reaction that has remained elusive for other histone chaperones, and it advances our understanding of how nucleosomes and their epigenetic information are maintained through DNA replication.
Article and author information
Author details
Francesca Mattiroli
Funding
Howard Hughes Medical Institute (Investigator)
- Karolin Luger
National Institute of General Medical Sciences (GM067777)
- Karolin Luger
European Molecular Biology Organization (ALTF 1267-2013)
- Francesca Mattiroli
KWF Kankerbestrijding (2014-6649)
- Francesca Mattiroli
National Science Foundation (MCB-1330019)
- Laurie A Stargell
National Institute of General Medical Sciences (GM114594)
- Natalie G Ahn
National Institute of General Medical Sciences (GM102253)
- Iestyn Whitehouse
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paul D. Kaufman, U. Massachusetts Medical School, United States
Version history
- Received: October 29, 2016
- Accepted: March 14, 2017
- Accepted Manuscript published: March 18, 2017 (version 1)
- Version of Record published: April 25, 2017 (version 2)
- Version of Record updated: February 12, 2018 (version 3)
Copyright
© 2017, Mattiroli et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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DNA-mediated association of two histone-bound CAF-1 complexes drives tetrasome assembly in the wake of DNA replication
eLife 6:e22799.
https://doi.org/10.7554/eLife.22799
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