| Literature DB >> 32015466 |
Chaoying Ni1,2, Wei Jiang1,2, Zhongju Wang1,2, Zhuo Wang2,3, Jian Zhang1, Xianzhen Zheng4, Zelin Liu5, Haiyan Ou1,2, Tingyun Jiang6, Wenquan Liang1, Fengchun Wu7, Qiyang Li1,2, Yu Hou1, Qiong Yang7, Bo Guo1,2, Sihan Liu8, Shuyun Li7, Shufen Li1,2, Ence Yang5, Xin-Hong Zhu2,3, Xingbing Huang7, Zhexing Wen9, Cunyou Zhao10,11.
Abstract
Schizophrenia is a complex genetic disorder, the non-Mendelian features of which are likely complicated by epigenetic factors yet to be elucidated. Here, we performed RNA sequencing of peripheral blood RNA from monozygotic twins discordant for schizophrenia, and identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA, AC006129.1) that participates in the inflammatory response by enhancing SOCS3 and CASP1 expression in schizophrenia patients and further validated this finding in AC006129.1-overexpressing mice showing schizophrenia-related abnormal behaviors. We find that AC006129.1 binds to the promoter region of the transcriptional repressor Capicua (CIC), facilitates the interactions of DNA methyltransferases with the CIC promoter, and promotes DNA methylation-mediated CIC downregulation, thereby ameliorating CIC-induced SOCS3 and CASP1 repression. Derepression of SOCS3 enhances the anti-inflammatory response by inhibiting JAK/STAT-signaling activation. Our findings reveal an epigenetic mechanism with etiological and therapeutic implications for schizophrenia.Entities:
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Year: 2020 PMID： 32015466 DOI： 10.1038/s41380-020-0662-3
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 15.992