DNA去甲基化
染色质
基因
生物
基因组
5-羟甲基胞嘧啶
基因表达
细胞生物学
遗传学
DNA甲基化
作者
Dongning Wu,Kaixin Huang,Junbo Shi,Sha Li,Wenjing Wang,Jiazhi Jiang,Hui Ping Ren,Tongyu Chen,Shengda Ye,Jincao Chen,Wei Wei,Xiang Li
标识
DOI:10.1021/acschemneuro.3c00554
摘要
An abundant accumulation of DNA demethylation intermediates has been identified in mammalian neurons. While the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neuronal function have been extensively studied, little is known about 5-formylcytosine (5fC) in neurons. Therefore, this study was to investigate the genome-wide distribution and potential functions of 5fC in neurons. In an in vitro culture model of mouse primary cortical neurons, we observed a dynamic increase in the total 5fC level in the neuronal genome after potassium chloride (KCl) stimulation. Subsequently, we employed chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to examine the 5fC distribution at a single-base resolution. Bioinformatic analysis revealed that 5fC was enriched in promoter regions, and gene ontology (GO) analysis indicated that the differential formylation positions (DFP) were correlated with neuronal activities. Additionally, integration with previously published nascent RNA-seq data revealed a positive correlation between gene formylation and mRNA expression levels. As well, 6 neuro-activity-related genes with a positive correlation were validated. Furthermore, we observed higher chromatin accessibility and RNA pol II binding signals near the 5fC sites through multiomics analysis. Motif analysis identified potential reader proteins for 5fC. In conclusion, our work provides a valuable resource for studying the dynamic changes and functional roles of 5fC in activated mammalian neurons.
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