G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 o...

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Published inNature communications Vol. 15; no. 1; pp. 1045 - 17
Main Authors Wang, Wenmeng, Li, Dangdang, Xu, Qingqing, Cheng, Jiahui, Yu, Zhiwei, Li, Guangyue, Qiao, Shiyao, Pan, Jiasong, Wang, Hao, Shi, Jinming, Zheng, Tongsen, Sui, Guangchao
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 05.02.2024
Nature Publishing Group
Nature Portfolio
Subjects
13/1
14/19
14/35
38/109
45/15
59
631/337/572/2102
631/57/2269
631/67/395
64/60
82/29
82/83
96
Binding
Bromodomain Containing Proteins
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell proliferation
Condensates
Cyclin D1 - genetics
Cyclin D1 - metabolism
DNA-Binding Proteins - metabolism
DNA-directed RNA polymerase
G-Quadruplexes
Gene expression
Hepatocellular carcinoma
Histones
Humanities and Social Sciences
Humans
Liver cancer
Motility
multidisciplinary
Nuclear Proteins - metabolism
Phase separation
RNA polymerase
RNA polymerase II
Science
Science (multidisciplinary)
Transcription factors
Transcription Factors - metabolism
Xenotransplantation
Zinc finger proteins
Zinc Fingers - genetics
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Abstract G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis. G-quadruplexes (G4s) can recruit transcription factors to activate genes. Here, the authors revealed that G4s drive molecular motility in phase-separated condensates of MAZ and coactivators, leading to activated CCND1 expression in liver cancer.
AbstractList Abstract G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.
G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis. G-quadruplexes (G4s) can recruit transcription factors to activate genes. Here, the authors revealed that G4s drive molecular motility in phase-separated condensates of MAZ and coactivators, leading to activated CCND1 expression in liver cancer.
G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.
G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.
G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.G-quadruplexes (G4s) can recruit transcription factors to activate genes. Here, the authors revealed that G4s drive molecular motility in phase-separated condensates of MAZ and coactivators, leading to activated CCND1 expression in liver cancer.
ArticleNumber 1045
Author Wang, Wenmeng
Zheng, Tongsen
Xu, Qingqing
Qiao, Shiyao
Li, Guangyue
Sui, Guangchao
Shi, Jinming
Cheng, Jiahui
Yu, Zhiwei
Li, Dangdang
Pan, Jiasong
Wang, Hao
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/38316778$$D View this record in MEDLINE/PubMed
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Snippet G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in...
Abstract G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate...
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SubjectTerms 13/1
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631/57/2269
631/67/395
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96
Binding
Bromodomain Containing Proteins
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell proliferation
Condensates
Cyclin D1 - genetics
Cyclin D1 - metabolism
DNA-Binding Proteins - metabolism
DNA-directed RNA polymerase
G-Quadruplexes
Gene expression
Hepatocellular carcinoma
Histones
Humanities and Social Sciences
Humans
Liver cancer
Motility
multidisciplinary
Nuclear Proteins - metabolism
Phase separation
RNA polymerase
RNA polymerase II
Science
Science (multidisciplinary)
Transcription factors
Transcription Factors - metabolism
Xenotransplantation
Zinc finger proteins
Zinc Fingers - genetics
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Title G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis
URI https://link.springer.com/article/10.1038/s41467-024-45353-5
https://www.ncbi.nlm.nih.gov/pubmed/38316778
https://www.proquest.com/docview/2922280525
https://www.proquest.com/docview/2922948508
https://pubmed.ncbi.nlm.nih.gov/PMC10844655
https://doaj.org/article/270e1586a19344b1abcaa51a6a6d0f85
Volume 15
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