論文 - 詳細
| RRC ID | 60961 |
|---|---|
| 著者 | Shen T, Ji F, Wang Y, Lei X, Zhang D, Jiao J. |
| タイトル | Brain-specific deletion of histone variant H2A.z results in cortical neurogenesis defects and neurodevelopmental disorder. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Defects in neurogenesis alter brain circuit formations and may lead to neurodevelopmental disorders such as autism and schizophrenia. Histone H2A.z, a variant of histone H2A, plays critical roles in chromatin structure and epigenetic regulation, but its function and mechanism in brain development remain largely unknown. Here, we find that the deletion of H2A.z results in enhanced proliferation of neural progenitors but reduced neuronal differentiation. In addition, neurons in H2A.z knockout mice exhibit abnormal dendrites during brain development. Furthermore, H2A.zcKO mice exhibit serial behavioral deficits, such as decreased exploratory activity and impaired learning and memory. Mechanistically, H2A.z regulates embryonic neurogenesis by targeting Nkx2-4 through interaction with Setd2, thereby promoting H3K36me3 modification to activate the transcription of Nkx2-4. Furthermore, enforced expression of Nkx2-4 can rescue the defective neurogenesis in the H2A.z-knockdown embryonic brain. Together, our findings implicate the epigenetic regulation by H2A.z in embryonic neurogenesis and provide a framework for understanding how disruption in the H2A.z gene may contribute to neurological disorders. |
| 巻・号 | 46(5) |
| ページ | 2290-2307 |
| 公開日 | 2018-3-16 |
| DOI | 10.1093/nar/gkx1295 |
| PII | 4780167 |
| PMID | 29294103 |
| PMC | PMC5861433 |
| MeSH | Animals Brain / embryology Brain / metabolism* Cell Line, Tumor Cerebral Cortex / embryology Cerebral Cortex / metabolism Gene Deletion* Gene Expression Profiling HEK293 Cells Histones / genetics* Histones / metabolism Humans Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neurodevelopmental Disorders / genetics* Neurodevelopmental Disorders / metabolism Neurogenesis / genetics* Organ Specificity / genetics* RNA Interference |
| IF | 11.502 |
| 引用数 | 15 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05765 |