Transcription factor POU3F2 regulates TRIM8 expression contributing to cellular functions implicated in schizophrenia
发布时间：2020-09-14
点击次数：
影响因子：12.4
DOI码：10.1038/s41380-020-00877-2
发表刊物：Molecular Psychiatry
摘要：Schizophrenia (SCZ) is a neuropsychiatric disorder with aberrant expression of multiple genes. However, identifying its exact causal genes remains a considerable challenge. The brain-specific transcription factor POU3F2 (POU domain, class 3, transcription factor 2) has been recognized as a risk factor for SCZ, but our understanding of its target genes and pathogenic mechanisms are still limited. Here we report that POU3F2 regulates 42 SCZ-related genes in knockdown and RNAsequencing experiments of human neural progenitor cells (NPCs). Among those SCZ-related genes, TRIM8 (Tripartite motif containing 8) is located in SCZ-associated genetic locus and is aberrantly expressed in patients with SCZ. Luciferase reporter and electrophoretic mobility shift assays (EMSA) showed that POU3F2 induces TRIM8 expression by binding to the SCZassociated SNP (single nucleotide polymorphism) rs5011218, which affects POU3F2-binding efficiency at the promoter region of TRIM8. We investigated the cellular functions of POU3F2 and TRIM8 as they co-regulate several pathways related to neural development and synaptic function. Knocking down either POU3F2 or TRIM8 promoted the proliferation of NPCs, inhibited their neuronal differentiation, and impaired the excitatory synaptic transmission of NPC-derived neurons. These results indicate that POU3F2 regulates TRIM8 expression through the SCZ-associated SNP rs5011218, and both genes may be involved in the etiology of SCZ by regulating neural development and synaptic function.
合写作者：Chunling Zhang, Richard Kopp, Liz Kuney, Qingtuan Meng, Le Wang, Yan Xia, Yi Jiang, Rujia Dai, Shishi Min, Wei-Dong Yao, Ma-Li Wong, Hongyu Ruan*, Chunyu Liu*, Chao Chen*
第一作者：Ding Chaodong
论文类型：文章
字数：8000
是否译文：否
发表时间：2020-09-14
收录刊物：SCI