DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity
Summary: Maternal-deposited factors initiate zygotic genome activation (ZGA), driving the maternal-to-zygotic transition; however, the coordination between maternal coactivators and transcription factors (TFs) in this process remains unclear. In this study, by profiling the dynamic landscape of p300...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003158 |
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| author | Lieying Xiao Hao Jin Yanna Dang Panpan Zhao Shuang Li Yan Shi Shaohua Wang Kun Zhang |
| author_facet | Lieying Xiao Hao Jin Yanna Dang Panpan Zhao Shuang Li Yan Shi Shaohua Wang Kun Zhang |
| author_sort | Lieying Xiao |
| collection | DOAJ |
| description | Summary: Maternal-deposited factors initiate zygotic genome activation (ZGA), driving the maternal-to-zygotic transition; however, the coordination between maternal coactivators and transcription factors (TFs) in this process remains unclear. In this study, by profiling the dynamic landscape of p300 during mouse ZGA, we reveal its role in promoting RNA polymerase II (Pol II) pre-configuration at ZGA gene regions and sequentially establishing enhancer activity and regulatory networks. Moreover, p300/CBP-catalyzed acetylation drives Pol II elongation and minor ZGA gene expression by inducing pivotal TFs such as Dux. Remarkably, the supplementation of exogenous Dux rescues ZGA failure and developmental defects caused by the loss of p300/CBP acetylation. DUX functions as a pioneer factor, guiding p300 and Pol II to minor ZGA gene regions and activating them in a manner dependent on the non-catalytic functions of p300/CBP. Together, our findings reveal a mutual dependency between p300/CBP and DUX, highlighting their coordinated role in regulating minor ZGA activation. |
| format | Article |
| id | doaj-art-29aef2b34c1542268ecdf17ebc7b238a |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-29aef2b34c1542268ecdf17ebc7b238a2025-08-20T02:16:29ZengElsevierCell Reports2211-12472025-04-0144411554410.1016/j.celrep.2025.115544DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activityLieying Xiao0Hao Jin1Yanna Dang2Panpan Zhao3Shuang Li4Yan Shi5Shaohua Wang6Kun Zhang7Laboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, ChinaLaboratory of Mammalian Molecular Embryology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China; Corresponding authorSummary: Maternal-deposited factors initiate zygotic genome activation (ZGA), driving the maternal-to-zygotic transition; however, the coordination between maternal coactivators and transcription factors (TFs) in this process remains unclear. In this study, by profiling the dynamic landscape of p300 during mouse ZGA, we reveal its role in promoting RNA polymerase II (Pol II) pre-configuration at ZGA gene regions and sequentially establishing enhancer activity and regulatory networks. Moreover, p300/CBP-catalyzed acetylation drives Pol II elongation and minor ZGA gene expression by inducing pivotal TFs such as Dux. Remarkably, the supplementation of exogenous Dux rescues ZGA failure and developmental defects caused by the loss of p300/CBP acetylation. DUX functions as a pioneer factor, guiding p300 and Pol II to minor ZGA gene regions and activating them in a manner dependent on the non-catalytic functions of p300/CBP. Together, our findings reveal a mutual dependency between p300/CBP and DUX, highlighting their coordinated role in regulating minor ZGA activation.http://www.sciencedirect.com/science/article/pii/S2211124725003158CP: Developmental biology |
| spellingShingle | Lieying Xiao Hao Jin Yanna Dang Panpan Zhao Shuang Li Yan Shi Shaohua Wang Kun Zhang DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity Cell Reports CP: Developmental biology |
| title | DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity |
| title_full | DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity |
| title_fullStr | DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity |
| title_full_unstemmed | DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity |
| title_short | DUX-mediated configuration of p300/CBP drives minor zygotic genome activation independent of its catalytic activity |
| title_sort | dux mediated configuration of p300 cbp drives minor zygotic genome activation independent of its catalytic activity |
| topic | CP: Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003158 |
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