Epigenomic landscapes during prefrontal cortex development and aging in rhesus  

作　　者：Chao Ning Xi Wu Xudong Zhao Zongyang Lu Xuelong Yao Tao Zhou Lizhi Yi Yaoyu Sun Shuaishuai Wu Zhenbo Liu Xingxu Huang Lei Gao Jiang Lu 

机构地区：[1]National Laboratory of Biomacro molecules,CAs Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [2]College of Life Sciences,University of Chinese Academy of Sciences,Bejing 100049,China [3]Division of HIV/AIDS and Sex-Transmitted Virus Vaccines,Institute for Biological Product Control,National Institutesfor Food and Drug Control(NIFDC),State Key Laboratory of Drug Regulatory Science,Beijing 102629,China [4]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academyof Sciences,Kunming Institute of Zoology,Chinese Academyof Sciences,Kunming 650223,China [5]School of Life Scienceand Technology,Shanghai Tech University,Shanghai 201210,China [6]Guangzhou Nvwa Life Technology Co.,Ltd,Guangzhou 510535,China [7]Shenzhen Neher Neural Plasticity Laboratory,CAS Key Laboratory of Brain Connectomeand Manipulation,The Brain Cognitionand Brain Disease Institute,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China [8]Key Laboratory of Epigenetic Regulation and Intervention,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [9]Zhejiang Provincial Key Laboratory of Pancreatic Disease,The First Affiliated Hospital,and Institute of Translational Medicine,Zhejiang University School of Medicine,Hangzhou 310058,China [10]Centerfor Excellencein Animal Evolutionand Genetics,Chinese Academy of Sciences,Kunming 650223,China

出　　处：《National Science Review》2024年第8期69-91,共23页国家科学评论（英文版）

基　　金：supported by the National Key Research and Development Program of China (2022YFC2703302 to L.G.);the Youth Innovation Promotion Association of the Chinese Academy of Sciences (202000001l to L.G.);the Outstanding Youth Fund of the Chinese Academy of Sciences (31425015 to J.L.);the National Natural Science Foundation of China (81671516 to X.H.);the Basic and Applied Basic Research Foundation of Guangdong Province (2019B151502007 to T.Z.).

摘　　要：The prefrontal cortex(PFC)is essential for higher-level cognitive functions.How epigenetic dynamics participates in PFC development and aging is largely unknown.Here,we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages.The dynamics of chromatin states including higher-order chromatin structure,chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription,participating in distinct processes of neurodevelopment.Dramatic changes of epigenetic signals occur around the birth stage.Notably,genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters.We identified a cis-regulatory module and the transcription factors(TFs)associated with basal radial glia development,which was associated with large brain size in primates.These TFs include GLI3,CREBS and SOX9.Interestingly,the genes associated with the basal radial glia(bRG)-associated cis-element module,such as SRY and SOX9,are enriched in sex differentiation.Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers(SEs)than typical enhancers,suggesting that SEs play an important role in neural network wiring.A cis-regulatory element of DBN1 is identified,which is critical for neuronal cell proliferation and synaptic neuron differentiation.Notably,the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging,which are associated with abnormal expression of aging-related genes and transposon activation,respectively.Collectively,our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

关 键 词：rhesus macaque prefrontal cortex 3D genomics chromatin immunoprecipitation sequencing DEVELOPMENT AGING 

分 类 号：Q4[生物学—生理学]