Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation
Summary: Genome-wide association studies (GWASs) have identified numerous genomic loci linked to schizophrenia (SCZ), while their pathogenic mechanisms largely remain unclear. This study demonstrated protein arginine methyltransferase 7 (PRMT7) as a key target of SCZ risk SNPs with allele-specific e...
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000506 |
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| author | Ting Shen Jing Yu Bin Xie Cuiping Huang Jingjie Cui Kefu Liu Chunyu Liu Chao Chen |
| author_facet | Ting Shen Jing Yu Bin Xie Cuiping Huang Jingjie Cui Kefu Liu Chunyu Liu Chao Chen |
| author_sort | Ting Shen |
| collection | DOAJ |
| description | Summary: Genome-wide association studies (GWASs) have identified numerous genomic loci linked to schizophrenia (SCZ), while their pathogenic mechanisms largely remain unclear. This study demonstrated protein arginine methyltransferase 7 (PRMT7) as a key target of SCZ risk SNPs with allele-specific enhancer activity at 16q22.1. Downregulating PRMT7 in neural progenitor cells (NPCs) decreased proliferation, increased neuronal differentiation, and also led to longer neurites in these neurons. Conversely, overexpressing PRMT7 enhanced NPC proliferation and reduced neuronal differentiation. In three-dimensional (3D) cerebral organoids, similar NPC phenotypic changes were noted following PRMT7 depletion. Mechanistically, PRMT7 regulates the expression of genes related to the cell cycle and neuronal functions, such as CDKN2A and SYP, via symmetrical di-methylation at arginine 3 of histone 4 (H4R3me2s) modification in their promoters. Notably, these genes have a stronger association with SCZ compared to other mental disorders. Together, the results of this study reveal that PRMT7 is a functional gene at 16q22.1, contributing to the etiology of SCZ by modulating NPC proliferation and differentiation as an epigenetic regulator. |
| format | Article |
| id | doaj-art-63348ea3b4a14e379b9558405e426031 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-63348ea3b4a14e379b9558405e4260312025-02-08T05:00:11ZengElsevierCell Reports2211-12472025-02-01442115279Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiationTing Shen0Jing Yu1Bin Xie2Cuiping Huang3Jingjie Cui4Kefu Liu5Chunyu Liu6Chao Chen7MOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, China; Corresponding authorMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, ChinaMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, ChinaMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, ChinaMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, ChinaMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, ChinaMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, China; Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USAMOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, and Department of Psychiatry, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, China; National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital, Central South University, Changsha 410000, Hunan, China; Furong Laboratory, Changsha 410000, Hunan, China; Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha 410000, China; Corresponding authorSummary: Genome-wide association studies (GWASs) have identified numerous genomic loci linked to schizophrenia (SCZ), while their pathogenic mechanisms largely remain unclear. This study demonstrated protein arginine methyltransferase 7 (PRMT7) as a key target of SCZ risk SNPs with allele-specific enhancer activity at 16q22.1. Downregulating PRMT7 in neural progenitor cells (NPCs) decreased proliferation, increased neuronal differentiation, and also led to longer neurites in these neurons. Conversely, overexpressing PRMT7 enhanced NPC proliferation and reduced neuronal differentiation. In three-dimensional (3D) cerebral organoids, similar NPC phenotypic changes were noted following PRMT7 depletion. Mechanistically, PRMT7 regulates the expression of genes related to the cell cycle and neuronal functions, such as CDKN2A and SYP, via symmetrical di-methylation at arginine 3 of histone 4 (H4R3me2s) modification in their promoters. Notably, these genes have a stronger association with SCZ compared to other mental disorders. Together, the results of this study reveal that PRMT7 is a functional gene at 16q22.1, contributing to the etiology of SCZ by modulating NPC proliferation and differentiation as an epigenetic regulator.http://www.sciencedirect.com/science/article/pii/S2211124725000506CP: Neuroscience |
| spellingShingle | Ting Shen Jing Yu Bin Xie Cuiping Huang Jingjie Cui Kefu Liu Chunyu Liu Chao Chen Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation Cell Reports CP: Neuroscience |
| title | Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation |
| title_full | Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation |
| title_fullStr | Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation |
| title_full_unstemmed | Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation |
| title_short | Protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation |
| title_sort | protein arginine methyltransferase 7 linked to schizophrenia through regulation of neural progenitor cell proliferation and differentiation |
| topic | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000506 |
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