遗传学报2024，Vol.51Issue(4) ：419-432.DOI:10.1016/j.jgg.2023.10.006

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

Qing Yang Qiang Cao Yue Yu Xianxin Lai Jiahao Feng Xinjie Li Yinan Jiang Yazhou Sun Zhong-Wei Zhou Xin Li
遗传学报2024，Vol.51Issue(4) ：419-432.DOI:10.1016/j.jgg.2023.10.006
✕
  • NETL
  • NSTL
  • 万方数据

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

Qing Yang 1Qiang Cao 2Yue Yu 2Xianxin Lai 2Jiahao Feng 2Xinjie Li 2Yinan Jiang 2Yazhou Sun 3Zhong-Wei Zhou 2Xin Li4
扫码查看

作者信息

  • 1. 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
  • 2. School of Medicine,Shenzhen Campus of Sun Yat-sen University,Shenzhen,Guangdong 518107,China
  • 3. School of Medicine,Shenzhen Campus of Sun Yat-sen University,Shenzhen,Guangdong 518107,China;Scientific Research Center,The Seventh Affiliated Hospital of Sun Yat-sen University,Shenzhen,Guangdong 518107,China
  • 4. School of Medicine,Shenzhen Campus 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
  • 折叠

Abstract

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.

Key words

Microcephaly/Epigenetic modification/Tet1/Cerebral cortex development/DNA hydroxymethylome/Transcriptome

引用本文复制引用

基金项目

National Natural Science Foundation of China(81872299)

National Natural Science Foundation of China(3217070538)

Shenzhen Science and Technology Program(JCYJ20190807160011600)

Shenzhen Science and Technology Program(JCYJ20210324124808023)

Shenzhen Science and Technology Program(JCYJ20200109142446804)

Shenzhen Science and Technology Program(JCYJ20220530145807018)

Shenzhen Science and Technology Program(ZDSYS2022060)

Guangdong Provincial Key Laboratory of Digestive Cancer Research(2021B1212040006)

China Postdoctoral science Foundation(2020M683073)

出版年

2024
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

CSTPCDCSCD
影响因子：0.821
ISSN：1673-8527
参考文献量56
段落导航相关论文