首页|Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model

Epigenetic and transcriptional landscapes during cerebral cortex development in a microcephaly mouse model

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The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous system.DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development.However,it remains unclear whether abnormal cerebral cortex development,such as microcephaly,could rescale the epigenetic landscape,potentially contributing to dysregulated gene expression during brain development.In this study,we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type(WT)mice and Mcph1 knockout(Mcph1-del)mice with severe microcephaly.Intriguingly,we discover a global reduction of 5'-hydroxymethylcytosine(5hmC)level,primarily in TET1-binding regions,in Mcph1-del mice compared to WT mice during juvenile and adult stages.Notably,genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions.Additionally,genes displaying a delayed accumulation of 5hmC in Mcph 1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage.These findings reveal that aberrant cerebral cortex development in the early stages profoundly alters the epigenetic regulation program,which provides unique insights into the molecular mechanisms under-pinning diseases related to cerebral cortex development.

MicrocephalyEpigenetic modificationTet1Cerebral cortex developmentDNA hydroxymethylomeTranscriptome

Qing Yang、Qiang Cao、Yue Yu、Xianxin Lai、Jiahao Feng、Xinjie Li、Yinan Jiang、Yazhou Sun、Zhong-Wei Zhou、Xin Li

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School of Medicine,Shenzhen Campus of Sun Yat-sen University,Shenzhen,Guangdong 518107,China

Academy of Medical Engineering and Translational Medicine,Tianjin University,Tianjin 300072,China

Scientific Research Center,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,Guangdong 518107,China

Guangdong Provincial Key Laboratory of Digestive Cancer Research,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,Guangdong 518107,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaShenzhen Science and Technology ProgramShenzhen Science and Technology ProgramShenzhen Science and Technology ProgramShenzhen Science and Technology ProgramShenzhen Science and Technology ProgramGuangdong Provincial Key Laboratory of Digestive Cancer ResearchChina Postdoctoral science Foundation

818722993217070538JCYJ20190807160011600JCYJ20210324124808023JCYJ20200109142446804JCYJ20220530145807018ZDSYS20220602021B12120400062020M683073

2024

10.1016/j.jgg.2023.10.006

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(4)
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