Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities
Summary: Appropriate histone modifications emerge as essential cell fate regulators of neuronal identities across neocortical areas and layers. Here we showed that NSD1, the methyltransferase for di-methylated lysine 36 of histone H3 (H3K36me2), controls both area and layer identities of the neocort...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723015085 |
| _version_ | 1797506300694757376 |
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| author | Yue Zheng Chen Zhao Qiulin Song Lichao Xu Bo Zhang Guangda Hu Xiangfei Kong Shaowen Li Xiang Li Yin Shen Lenan Zhuang Min Wu Ying Liu Yan Zhou |
| author_facet | Yue Zheng Chen Zhao Qiulin Song Lichao Xu Bo Zhang Guangda Hu Xiangfei Kong Shaowen Li Xiang Li Yin Shen Lenan Zhuang Min Wu Ying Liu Yan Zhou |
| author_sort | Yue Zheng |
| collection | DOAJ |
| description | Summary: Appropriate histone modifications emerge as essential cell fate regulators of neuronal identities across neocortical areas and layers. Here we showed that NSD1, the methyltransferase for di-methylated lysine 36 of histone H3 (H3K36me2), controls both area and layer identities of the neocortex. Nsd1-ablated neocortex showed an area shift of all four primary functional regions and aberrant wiring of cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning, and coordination, resembling patients with the Sotos syndrome carrying NSD1 mutations. On Nsd1 loss, superficial-layer pyramidal neurons (PNs) progressively mis-expressed markers for deep-layer PNs, and PNs remained immature both morphologically and electrophysiologically. Loss of Nsd1 in postmitotic PNs causes genome-wide loss of H3K36me2 and re-distribution of DNA methylation, which accounts for diminished expression of neocortical layer specifiers but ectopic expression of non-neural genes. Together, H3K36me2 mediated by NSD1 is required for the establishment and maintenance of region- and layer-specific neocortical identities. |
| first_indexed | 2024-03-10T04:30:42Z |
| format | Article |
| id | doaj.art-4b315c1760b44f0b80274e82fb941a82 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-10T04:30:42Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4b315c1760b44f0b80274e82fb941a822023-11-23T04:28:17ZengElsevierCell Reports2211-12472023-12-014212113496Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identitiesYue Zheng0Chen Zhao1Qiulin Song2Lichao Xu3Bo Zhang4Guangda Hu5Xiangfei Kong6Shaowen Li7Xiang Li8Yin Shen9Lenan Zhuang10Min Wu11Ying Liu12Yan Zhou13Department of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaFrontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China; Eye Center, Wuhan University Renmin Hospital, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, ChinaFrontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China; Eye Center, Wuhan University Renmin Hospital, Wuhan 430071, ChinaDepartment of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, ChinaFrontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China; College of Life Sciences, Taikang Center for Life and Medical Sciences of Wuhan University, Wuhan 430071, China; Corresponding authorDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China; Corresponding authorDepartment of Neurosurgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China; Frontier Science Center of Immunology and Metabolism, Wuhan University, Wuhan 430071, China; Corresponding authorSummary: Appropriate histone modifications emerge as essential cell fate regulators of neuronal identities across neocortical areas and layers. Here we showed that NSD1, the methyltransferase for di-methylated lysine 36 of histone H3 (H3K36me2), controls both area and layer identities of the neocortex. Nsd1-ablated neocortex showed an area shift of all four primary functional regions and aberrant wiring of cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning, and coordination, resembling patients with the Sotos syndrome carrying NSD1 mutations. On Nsd1 loss, superficial-layer pyramidal neurons (PNs) progressively mis-expressed markers for deep-layer PNs, and PNs remained immature both morphologically and electrophysiologically. Loss of Nsd1 in postmitotic PNs causes genome-wide loss of H3K36me2 and re-distribution of DNA methylation, which accounts for diminished expression of neocortical layer specifiers but ectopic expression of non-neural genes. Together, H3K36me2 mediated by NSD1 is required for the establishment and maintenance of region- and layer-specific neocortical identities.http://www.sciencedirect.com/science/article/pii/S2211124723015085CP: NeuroscienceCP: Molecular biology |
| spellingShingle | Yue Zheng Chen Zhao Qiulin Song Lichao Xu Bo Zhang Guangda Hu Xiangfei Kong Shaowen Li Xiang Li Yin Shen Lenan Zhuang Min Wu Ying Liu Yan Zhou Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities Cell Reports CP: Neuroscience CP: Molecular biology |
| title | Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities |
| title_full | Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities |
| title_fullStr | Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities |
| title_full_unstemmed | Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities |
| title_short | Histone methylation mediated by NSD1 is required for the establishment and maintenance of neuronal identities |
| title_sort | histone methylation mediated by nsd1 is required for the establishment and maintenance of neuronal identities |
| topic | CP: Neuroscience CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723015085 |
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