NFIB facilitates replication licensing by acting as a genome organizer
© 2023. Springer Nature Limited..
The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 21. Aug., Seite 5076 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Wenting [VerfasserIn] |
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| Links: |
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| Themen: |
Chromatin |
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| Anmerkungen: |
Date Completed 28.08.2023 Date Revised 18.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-40846-1 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes | ||
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| 700 | 1 | |a Wang, Yue |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yongjie |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Cuifang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yizhou |e verfasserin |4 aut | |
| 700 | 1 | |a He, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Yani |e verfasserin |4 aut | |
| 700 | 1 | |a Xia, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiaodi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jiajing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Luyang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guohong |e verfasserin |4 aut | |
| 700 | 1 | |a Tu, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Yongfeng |e verfasserin |4 aut | |
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