Affiliation:
1. Key Laboratory of Metabolism and Molecular Medicine of Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences Fudan University 200032 130 Dong An Road Shanghai China
2. Shengli Clinical Medical College of Fujian Medical University, Center for Experimental Research in Clinical Medicine Fujian Provincial Hospital 134 East Street Fuzhou 350001 China
Abstract
AbstractLysine demethylase KDM7A removes histone modifications H3K9me1/2 and H3K27me1/2. KDM7A plays critical roles in gene expression and contribute to biological processes including tumorigenesis, metabolism, and embryonic development. However, the functions of KDM7A in mammalian nervous system are still poorly explored. In this study, functional roles of KDM7A are comprehensively investigated in neuronal cells by applying CUT&Tag‐seq, RNA‐seq and mice models. Knockdown of Kdm7a in N2A cells result in the alteration of histone modifications near transcription start sites (TSSs) and the expression changes of a large number of genes. In particular, the expression of immediate early genes (IEGs), a series of genes maintaining the function of the nervous system and associating with neurological disorders, are significantly decreased upon Kdm7a knockdown. Furthermore, in vivo knockdown of Kdm7a in dentate gyrus (DG) neuron of mice hippocampus, via Adeno‐associated virus (AAV)‐based stereotaxic microinjection, led to a significant decrease of the expression of c‐Fos, a marker of neuron activity. Behavior assays in mice further revealed that Kdm7a knockdown in hippocampus repress neuron activity, which leading to impairment of emotion and memory. Collectively, the study reveals that KDM7A affects neuron functions by regulating IEGs, which may provide new clues for understanding epigenetic mechanisms in neurological disorders.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Natural Science Foundation of Fujian Province
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)