DNA methylation confers a cerebellum-specific identity in non-human primatesOACSCDCSTPCD
Selective regulation of gene expression across distinct brain regions is crucial for establishing and maintaining subdivision identities.DNA methylation,a key regulator of gene transcription,modulates transcriptional activity through the conversion of 5-methylcytosine(5mC)to 5-hydroxymethylcytosine(5hmC).While DNA methylation is hypothesized to play an essential role in shaping brain identity by influencing gene expression patterns,its direct contribution,especially in primates,remains largely unexplored.This study examined DNA methylation landscapes and transcriptional profiles across four brain regions,including the cortex,cerebellum,striatum,and hippocampus,using samples from 12 rhesus monkeys.The cerebellum exhibited distinct epigenetic and transcriptional signatures,with differentially methylated regions(DMRs)significantly enriched in metabolic pathways.Notably,genes harboring clustered differentially hydroxymethylated regions(DhMRs)overlapped with those implicated in schizophrenia.Moreover,5mC located1 kb upstream of the ATG start codon was correlated with gene expression and exhibited region-specific associations with 5hmC.These findings provide insights into the coordinated regulation of cerebellum-specific 5mC and5hmC,highlighting their potential roles in defining cerebellar identity and contributing to neuropsychiatric diseases.
Xiao-Dong Liu;Chang-Cheng Ye;Yang Wang;Xiao-Song Zhang;Hui-Xian Wei;Lei-Jie Xie;Jia-Xiang Xie;Yan-Ru Xu;Li-Ying Zhong;Shi-Hua Li;Xiao-Jiang Li;Li Lin
Guangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,ChinaGuangdong Key Laboratory of Non-human Primate Research,Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan University,Key Laboratory of CNS Regeneration(Jinan University)-Ministry of Education,Guangzhou,Guangdong 510632,China
生物科学
5-MethylcytosineGene expression5-HydroxymethylcytosineNon-human primatesCerebellumTissue identity
《Zoological Research》 2025 (2)
P.414-428,15
supported by the Natural Science Foundation of Guangdong Province(2022A1515010689)National Natural Science Foundation of China(82394422,82371874,82071421,82271902)Department of Science and Technology of Guangdong Province(2021ZT09Y007,2020B121201006)。
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