Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway
文献类型:期刊论文
作者 | Chen, Xuemei1,2,3,4; Wang, Shuai1,2; Zhou, Ying1,2; Han, Yanfei1,2,5,6; Li, Shengtian1,2; Song, Lulu1,2; He, Guang1,2; He, Lin1,2; Li, Weidong1,2; Xu, Qing3 |
刊名 | NATURE COMMUNICATIONS |
出版日期 | 2018 |
卷号 | 9期号:1页码:114 |
ISSN号 | 2041-1723 |
关键词 | Linked Mental-retardation Cleft lip/Cleft Palate Synaptic Plasticity Protein-synthesis Cell-cycle Gene Mutations Memory Identification Differentiation |
DOI | 10.1038/s41467-017-02531-y |
文献子类 | Article |
英文摘要 | Epigenomic abnormalities caused by genetic mutation in epigenetic regulators can result in neurodevelopmental disorders, deficiency in neural plasticity and mental retardation. As a histone demethylase, plant homeodomain finger protein 8 (Phf8) is a candidate gene for syndromal and non-specific forms of X-chromosome-linked intellectual disability (XLID). Here we report that Phf8 knockout mice displayed impaired learning and memory, and impaired hippocampal long-term potentiation (LTP) without gross morphological defects. We also show that mTOR signaling pathway is hyperactive in hippocampus in Phf8 knockout mouse. Mechanistically, we show that demethylation of H4K20me1 by Phf8 results in transcriptional suppression of RSK1 and homeostasis of mTOR signaling. Pharmacological suppression of mTOR signaling with rapamycin in Phf8 knockout mice recovers the weakened LTP and cognitive deficits. Together, our results indicate that loss of Phf8 in animals causes deficient learning and memory by epigenetic disruption of mTOR signaling, and provides a potential therapeutic drug target to treat XLID. |
WOS研究方向 | Multidisciplinary Sciences |
语种 | 英语 |
WOS记录号 | WOS:000419658100013 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/3450] |
专题 | 生化所2018年发文 上海生化细胞研究所_上海生科院生化细胞研究所 |
通讯作者 | Li, Weidong; Chen, Charlie Degui |
作者单位 | 1.Shanghai Jiao Tong Univ, Minist Educ, BioX Inst, Key Lab Genet Dev & Neuropsychiatr Disorders, 800 Dongchuan Rd, Shanghai 200240, Peoples R China; 2.Shanghai Jiao Tong Univ, Brain Sci & Technol Res Ctr, 800 Dongchuan Rd, Shanghai 200240, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Key Lab Mol Androl, State Key Lab Mol Biol,Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Ren Ji Hosp, Dept Anesthesiol, Shanghai 200127, Peoples R China; 5.Shanghai Jiao Tong Univ, Discipline Neurosci, Sch Med, Shanghai 200025, Peoples R China; 6.Shanghai Jiao Tong Univ, Sch Med, Dept Anat & Physiol, Shanghai 200025, Peoples R China; 7.Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA; 8.Univ N Carolina, Sch Med, Neurosci Ctr, Chapel Hill, NC 27514 USA; 9.RIKEN, Brain Sci Inst, Res Resources Ctr, 2-1 Hirosawa, Wako, Saitama 3510198, Japan |
推荐引用方式 GB/T 7714 | Chen, Xuemei,Wang, Shuai,Zhou, Ying,et al. Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway[J]. NATURE COMMUNICATIONS,2018,9(1):114. |
APA | Chen, Xuemei.,Wang, Shuai.,Zhou, Ying.,Han, Yanfei.,Li, Shengtian.,...&Takahashi, Eiki.(2018).Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway.NATURE COMMUNICATIONS,9(1),114. |
MLA | Chen, Xuemei,et al."Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway".NATURE COMMUNICATIONS 9.1(2018):114. |
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