Spt6 is a maintenance factor for centromeric CENP-A

Georg O. M. Bobkov, Anming Huang, Sebastiaan J. W. Berg, Sreyoshi Mitra, Eduard Anselm, Vasiliki Lazou, Sarah Schunter, Regina Feederle, Axel Imhof, Alexandra Lusser, Lars E. T. Jansen and Patrick Heun ()
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Georg O. M. Bobkov: The University of Edinburgh
Anming Huang: Medical University of Innsbruck
Sebastiaan J. W. Berg: Instituto Gulbenkian de Ciência
Sreyoshi Mitra: Instituto Gulbenkian de Ciência
Eduard Anselm: The University of Edinburgh
Vasiliki Lazou: The University of Edinburgh
Sarah Schunter: LMU
Regina Feederle: German Research Center for Environmental Health (GmbH)
Axel Imhof: Ludwig-Maximilians-University of Munich
Alexandra Lusser: Medical University of Innsbruck
Lars E. T. Jansen: University of Oxford
Patrick Heun: The University of Edinburgh

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centromere-specific histone dCENP-A in M/G1 phase, which depends on the eviction of previously deposited H3/H3.3-placeholder nucleosomes. Here we demonstrate that the histone chaperone and transcription elongation factor Spt6 spatially and temporarily coincides with centromeric transcription and prevents the loss of old CENP-A nucleosomes in both Drosophila and human cells. Spt6 binds directly to dCENP-A and dCENP-A mutants carrying phosphomimetic residues alleviate this association. Retention of phosphomimetic dCENP-A mutants is reduced relative to wildtype, while non-phosphorylatable dCENP-A retention is increased and accumulates at the centromere. We conclude that Spt6 acts as a conserved CENP-A maintenance factor that ensures long-term stability of epigenetic centromere identity during transcription-mediated chromatin remodeling.

Date: 2020
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DOI: 10.1038/s41467-020-16695-7

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