Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation.
Animals
CCAAT-Enhancer-Binding Proteins
/ metabolism
Chromatin
/ metabolism
DNA (Cytosine-5-)-Methyltransferase 1
/ metabolism
DNA Methylation
/ genetics
Humans
Male
Mice
Mouse Embryonic Stem Cells
/ metabolism
Protein Binding
Spermatozoa
/ metabolism
Ubiquitin-Protein Ligases
/ metabolism
Ubiquitination
Xenopus laevis
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
06 03 2020
06 03 2020
Historique:
received:
24
04
2019
accepted:
10
02
2020
entrez:
8
3
2020
pubmed:
8
3
2020
medline:
24
6
2020
Statut:
epublish
Résumé
Stable inheritance of DNA methylation is critical for maintaining differentiated phenotypes in multicellular organisms. We have recently identified dual mono-ubiquitylation of histone H3 (H3Ub2) by UHRF1 as an essential mechanism to recruit DNMT1 to chromatin. Here, we show that PCNA-associated factor 15 (PAF15) undergoes UHRF1-dependent dual mono-ubiquitylation (PAF15Ub2) on chromatin in a DNA replication-coupled manner. This event will, in turn, recruit DNMT1. During early S-phase, UHRF1 preferentially ubiquitylates PAF15, whereas H3Ub2 predominates during late S-phase. H3Ub2 is enhanced under PAF15 compromised conditions, suggesting that H3Ub2 serves as a backup for PAF15Ub2. In mouse ES cells, loss of PAF15Ub2 results in DNA hypomethylation at early replicating domains. Together, our results suggest that there are two distinct mechanisms underlying replication timing-dependent recruitment of DNMT1 through PAF15Ub2 and H3Ub2, both of which are prerequisite for high fidelity DNA methylation inheritance.
Identifiants
pubmed: 32144273
doi: 10.1038/s41467-020-15006-4
pii: 10.1038/s41467-020-15006-4
pmc: PMC7060239
doi:
Substances chimiques
CCAAT-Enhancer-Binding Proteins
0
Chromatin
0
DNA (Cytosine-5-)-Methyltransferase 1
EC 2.1.1.37
UHRF1 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1222Références
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