Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation
Copyright © 2021, American Association for the Advancement of Science..
Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo. These data reveal mechanisms that control H3K79 methylation and demonstrate how H4K16ac, H3K79me, and H2BUb function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state.
| Errataetall: |
CommentIn: Trends Biochem Sci. 2021 Jul;46(7):522-524. - PMID 33879367 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:371 |
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| Enthalten in: |
Science (New York, N.Y.) - 371(2021), 6527 vom: 22. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Valencia-Sánchez, Marco Igor [VerfasserIn] |
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| Links: |
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| Themen: |
Dot1 protein, S cerevisiae |
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| Anmerkungen: |
Date Completed 25.02.2021 Date Revised 04.08.2021 published: Print CommentIn: Trends Biochem Sci. 2021 Jul;46(7):522-524. - PMID 33879367 Citation Status MEDLINE |
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| doi: |
10.1126/science.abc6663 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320413993 |
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| 245 | 1 | 0 | |a Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021, American Association for the Advancement of Science. | ||
| 520 | |a Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trimethylation in vitro and in vivo. These data reveal mechanisms that control H3K79 methylation and demonstrate how H4K16ac, H3K79me, and H2BUb function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 7 | |a Nuclear Proteins |2 NLM | |
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| 700 | 1 | |a De Ioannes, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Miao |e verfasserin |4 aut | |
| 700 | 1 | |a Truong, David M |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Armache, Jean-Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Boeke, Jef D |e verfasserin |4 aut | |
| 700 | 1 | |a Armache, Karim-Jean |e verfasserin |4 aut | |
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