An EED/PRC2‐H19 Loop Regulates Cerebellar Development
Abstract EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem c...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202403591 |
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| author | Pei‐Pei Liu Xiao Han Xiao Li Shang‐Kun Dai Ya‐Jie Xu Lin‐Fei Jiao Hong‐Zhen Du Li‐Hua Zhao Rong‐Feng Li Zhao‐Qian Teng Yun‐Gui Yang Chang‐Mei Liu |
| author_facet | Pei‐Pei Liu Xiao Han Xiao Li Shang‐Kun Dai Ya‐Jie Xu Lin‐Fei Jiao Hong‐Zhen Du Li‐Hua Zhao Rong‐Feng Li Zhao‐Qian Teng Yun‐Gui Yang Chang‐Mei Liu |
| author_sort | Pei‐Pei Liu |
| collection | DOAJ |
| description | Abstract EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem cells (NSCs) or cerebellar granule cell progenitors (GCPs) leads to reduced GCPs proliferation, cell death, cerebellar hypoplasia, and motor deficits in mice. Joint profiling of transcripts and ChIP‐seq analysis in cerebellar granule cells reveals that EED regulates bunches of genes involved in cerebellar development. EED ablation exhibits overactivation of a developmental repressor long non‐coding RNA H19. Importantly, an obvious H3K27ac enrichment is found at Ctcf, a trans‐activator of H19, and H3K27me3 enrichment at the H19 imprinting control region (ICR), suggesting that EED regulates H19 in an H3K27me3‐dependent manner. Intriguingly, H19 deletion reduces EED expression and the reprogramming of EED‐mediated H3K27me3 profiles, resulting in increased proliferation, differentiation, and decreased apoptosis of GCPs. Finally, molecular and genetic evidence provides that increased H19 expression is responsible for cerebellar hypoplasia and motor defects in EED mutant mice. Thus, this study demonstrates that EED, H19 forms a negative feedback loop, which plays a crucial role in cerebellar morphogenesis and controls cerebellar development. |
| format | Article |
| id | doaj-art-fe93b287644944a5ab51c2e2121a3a21 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-fe93b287644944a5ab51c2e2121a3a212025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202403591An EED/PRC2‐H19 Loop Regulates Cerebellar DevelopmentPei‐Pei Liu0Xiao Han1Xiao Li2Shang‐Kun Dai3Ya‐Jie Xu4Lin‐Fei Jiao5Hong‐Zhen Du6Li‐Hua Zhao7Rong‐Feng Li8Zhao‐Qian Teng9Yun‐Gui Yang10Chang‐Mei Liu11Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaUniversity of Chinese Academy of Sciences Beijing 100049 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaJiangsu Key Laboratory of Xenotransplantation Nanjing Medical University Nanjing 211166 ChinaJiangsu Key Laboratory of Xenotransplantation Nanjing Medical University Nanjing 211166 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaUniversity of Chinese Academy of Sciences Beijing 100049 ChinaKey Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 ChinaAbstract EED (embryonic ectoderm development) is a core subunit of the polycomb repressive complex 2 (PRC2), which senses the trimethylation of histone H3 lysine 27 (H3K27). However, its biological function in cerebellar development remains unknown. Here, we show that EED deletion from neural stem cells (NSCs) or cerebellar granule cell progenitors (GCPs) leads to reduced GCPs proliferation, cell death, cerebellar hypoplasia, and motor deficits in mice. Joint profiling of transcripts and ChIP‐seq analysis in cerebellar granule cells reveals that EED regulates bunches of genes involved in cerebellar development. EED ablation exhibits overactivation of a developmental repressor long non‐coding RNA H19. Importantly, an obvious H3K27ac enrichment is found at Ctcf, a trans‐activator of H19, and H3K27me3 enrichment at the H19 imprinting control region (ICR), suggesting that EED regulates H19 in an H3K27me3‐dependent manner. Intriguingly, H19 deletion reduces EED expression and the reprogramming of EED‐mediated H3K27me3 profiles, resulting in increased proliferation, differentiation, and decreased apoptosis of GCPs. Finally, molecular and genetic evidence provides that increased H19 expression is responsible for cerebellar hypoplasia and motor defects in EED mutant mice. Thus, this study demonstrates that EED, H19 forms a negative feedback loop, which plays a crucial role in cerebellar morphogenesis and controls cerebellar development.https://doi.org/10.1002/advs.202403591cerebellumEED, H19, Motor movement, PRC2 |
| spellingShingle | Pei‐Pei Liu Xiao Han Xiao Li Shang‐Kun Dai Ya‐Jie Xu Lin‐Fei Jiao Hong‐Zhen Du Li‐Hua Zhao Rong‐Feng Li Zhao‐Qian Teng Yun‐Gui Yang Chang‐Mei Liu An EED/PRC2‐H19 Loop Regulates Cerebellar Development Advanced Science cerebellum EED, H19, Motor movement, PRC2 |
| title | An EED/PRC2‐H19 Loop Regulates Cerebellar Development |
| title_full | An EED/PRC2‐H19 Loop Regulates Cerebellar Development |
| title_fullStr | An EED/PRC2‐H19 Loop Regulates Cerebellar Development |
| title_full_unstemmed | An EED/PRC2‐H19 Loop Regulates Cerebellar Development |
| title_short | An EED/PRC2‐H19 Loop Regulates Cerebellar Development |
| title_sort | eed prc2 h19 loop regulates cerebellar development |
| topic | cerebellum EED, H19, Motor movement, PRC2 |
| url | https://doi.org/10.1002/advs.202403591 |
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