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Bobkov, G.O.M.* ; Huang, A.* ; van den Berg, S.J.W.* ; Mitra, S.* ; Anselm, E.* ; Lazou, V.* ; Schunter, S.* ; Feederle, R. ; Imhof, A.* ; Lusser, A.* ; Jansen, L.E.T.* ; Heun, P.*

Spt6 is a maintenance factor for centromeric CENP-A.

Nat. Commun. 11:2919 (2020)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Rna-polymerase-ii; Transcription Elongation; Drosophila; Chromatin; Nucleosome; Phosphorylation; Identification; Deposition; Mechanism; Histones
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 2919 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502210-001
DOI 10.1038/s41467-020-16695-7
WOS ID WOS:000543968400002
Scopus ID 85086319013
Erfassungsdatum 2020-06-19
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