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Santos-Rosa, H.* ; Millán-Zambrano, G.* ; Han, N.* ; Leonardi, T.* ; Klimontova, M.* ; Nasiscionyte, S. ; Pandolfini, L.* ; Tzelepis, K.* ; Bartke, T. ; Kouzarides, T.*

Methylation of histone H3 at lysine 37 by Set1 and Set2 prevents spurious DNA replication.

Mol. Cell 81, 2793-2807.e8 (2021)
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Free by publisher: Publ. Version/Full Text online available 06/2022
DNA replication initiates at genomic locations known as origins of replication, which, in S. cerevisiae, share a common DNA consensus motif. Despite being virtually nucleosome-free, origins of replication are greatly influenced by the surrounding chromatin state. Here, we show that histone H3 lysine 37 mono-methylation (H3K37me1) is catalyzed by Set1p and Set2p and that it regulates replication origin licensing. H3K37me1 is uniformly distributed throughout most of the genome, but it is scarce at replication origins, where it increases according to the timing of their firing. We find that H3K37me1 hinders Mcm2 interaction with chromatin, maintaining low levels of MCM outside of conventional replication origins. Lack of H3K37me1 results in defective DNA replication from canonical origins while promoting replication events at inefficient and non-canonical sites. Collectively, our results indicate that H3K37me1 ensures correct execution of the DNA replication program by protecting the genome from inappropriate origin licensing and spurious DNA replication.
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Publication type Article: Journal article
Document type Scientific Article
Keywords H3k37methylation ; Histone Modifications ; Mcm ; Origin Licensing ; Replication Origins ; Set1 ; Set2; Compass Family; Origin; Initiation; Proteins; Yeast; Acetylation; Chromatin; Program; Methyltransferase; Reveals
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Journal Molecular Cell
Quellenangaben Volume: 81, Issue: 13, Pages: 2793-2807.e8 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Grants Helmholtz Association
European Research Council (ERC)
Sir Henry Wellcome Fellowship
Asociacion Espanola Contra el Cancer
European Molecular Biology Organization (EMBO)
Wellcome Trust
Cancer Research UK