Epigenomic landscapes during prefrontal cortex development and aging in rhesus

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外文摘要：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,CREB5 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.

外文关键词：

rhesus macaqueprefrontal cortex3D genomicschromatin immunoprecipitation sequencingdevelopmentaging

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 Liu

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作者单位：

National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

College of Life Sciences,University of Chinese Academy of Sciences,Beijing 100049,China

National Laboratory of Biomacro-molecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

Division of HIV/AIDS and Sex-Transmitted Virus Vaccines,Institute for Biological Product Control,National Institutes for Food and Drug Control(NIFDC),State Key Laboratory of Drug Regulatory Science,Beijing 102629,China

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China

School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China

Guangzhou Nvwa Life Technology Co.,Ltd,Guangzhou 510535,China

Shenzhen Neher Neural Plasticity Laboratory,CAS Key Laboratory of Brain Connectome and Manipulation,The Brain Cognition and Brain Disease Institute,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China

Key Laboratory of Epigenetic Regulation and Intervention,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

School of Life Science and Technology,Shanghai Tech University,Shanghai 201210,China

Zhejiang Provincial Key Laboratory of Pancreatic Disease,The First Affiliated Hospital,and Institute of Translational Medicine,Zhejiang University School of Medicine,Hangzhou 310058,China

Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming 650223,China

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基金：

National Key Research and Development Program of ChinaYouth Innovation Promotion Association of the Chinese Academy of SciencesOutstanding Youth Fund of the Chinese Academy of SciencesNational Natural Science Foundation of ChinaBasic and Applied Basic Research Foundation of Guangdong Province

项目编号：

2022YFC2703302202000001131425015816715162019B151502007

出版年：

2024

DOI：

10.1093/nsr/nwae213

国家科学评论(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.11(8)

参考文献量1