Centromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition
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ncomms15775.pdf
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Author(s)
Guo, Lucie Y.
Allu, Praveen Kumar
Zandarashvili, Levani
Sekulic, Nikolina
Dawicki-McKenna, Jennine M.
Fachinetti, Daniele
Logsdon, Glennis A.
Jamiolkowski, Ryan M.
Cleveland, Don W.
Black, Ben E.
Date Issued
June 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Guo, Lucie Y. et al. “Centromeres Are Maintained by Fastening CENP-A to DNA and Directing an Arginine Anchor-Dependent Nucleosome Transition.” Nature Communications 8 (June 2017): 15775 © 2017 The Author(s)
Version
Final published version
Abstract
Maintaining centromere identity relies upon the persistence of the epigenetic mark provided by the histone H3 variant, centromere protein A (CENP-A), but the molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define the contributions of each of the three candidate CENP-A nucleosome-binding domains (two on CENP-C and one on CENP-N) to CENP-A stability using gene replacement and rapid protein degradation. Surprisingly, the most conserved domain, the CENP-C motif, is dispensable. Instead, the stability is conferred by the unfolded central domain of CENP-C and the folded N-terminal domain of CENP-N that becomes rigidified 1,000-fold upon crossbridging CENP-A and its adjacent nucleosomal DNA. Disrupting the 'arginine anchor' on CENP-C for the nucleosomal acidic patch disrupts the CENP-A nucleosome structural transition and removes CENP-A nucleosomes from centromeres. CENP-A nucleosome retention at centromeres requires a core centromeric nucleosome complex where CENP-C clamps down a stable nucleosome conformation and CENP-N fastens CENP-A to the DNA. Keywords: centromeres; supramolecular assembly
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/NCOMMS15775
