Spt6 is a maintenance factor for centromeric CENP-A

Georg Bobkov, Anming Huang, Sebastiaan J. W van den Berg, Sreyoshi Mitra, Eduard Anselm, Vasiliki Lazou, Sarah Schunter, Regina Feederle, Axel Imhof, Alexandra Lusser, Lars E T Jansen, Patrick Heun

Research output: Contribution to journalArticlepeer-review

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 andaccumulates 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.
Original languageEnglish
Article number2919
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 10 Jun 2020

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