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

Journal of Genetics and Genomics 2024年第4期51卷 419-432页

作者： Qing Yang Qiang Cao Yue Yu Xianxin Lai Jiahao Feng Xinjie Li Yinan Jiang Yazhou Sun Zhong-Wei Zhou Xin Li School of Medicine Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdong 518107China Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjin 300072China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

The cerebral cortex is a pivotal structure integral to advanced brain functions within the mammalian central nervous *** methylation and hydroxymethylation play important roles in regulating cerebral cortex ***,it remains unclear whether abnormal cerebral cortex development,such as microcephaly,could rescale the epigenetic landscape,potentially contributing to dysregulated gene expression during brain *** 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 ***,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 ***,genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain ***,genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult *** 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 underpinning diseases related to cerebral cortex development.

关键词： Microcephaly epigeneticmodification Tet1 Cerebral cortexdevelopment DNA hydroxymethylome Transcriptome

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