Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation
| Autor: | Yasushi Saeki, Carina Trummer, Akinori Endo, Sebastian Bultmann, Soichiro Kumamoto, Kyohei Arita, Atsuya Nishiyama, Genta Nagae, Makoto Nakanishi, Heinrich Leonhardt, Satomi Kori, Weihua Qin, Haruka Yokoyama, Hiroyuki Aburatani, Yoshie Chiba, Christopher B. Mulholland, Keiji Tanaka, Toru Kawakami, Hironobu Hojo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Male 0301 basic medicine Ubiquitin-Protein Ligases Science General Physics and Astronomy environment and public health Article General Biochemistry Genetics and Molecular Biology Mice Xenopus laevis 03 medical and health sciences Histone H3 0302 clinical medicine Ubiquitin Animals Humans lcsh:Science DNA methylation Multidisciplinary biology urogenital system Ubiquitination Mouse Embryonic Stem Cells SAXS General Chemistry Spermatozoa Phenotype Chromatin Cell biology Multicellular organism 030104 developmental biology embryonic structures CCAAT-Enhancer-Binding Proteins DNMT1 biology.protein lcsh:Q 030217 neurology & neurosurgery Protein Binding DNA hypomethylation |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-17 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Ubiquitylation of histone H3 (H3Ub2) by UHRF1 recruits DNMT1 to chromatin, which is essential for DNA methylation inheritance. Here, the authors provide evidence that there are two distinct mechanisms underlying replication timing-dependent recruitment of DNMT1 through PAF15Ub2 and H3Ub2, both of which are required for high fidelity DNA methylation inheritance. |
| Databáze: | OpenAIRE |
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