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论文题目: Brain-Specific Deletion of Histone Variant H2A.z Results in Cortical Neurogenesis Defects and Neurodevelopmental Disorder
论文题目英文:
作者: 沈天津,季芬,王媛媛,雷雪裴,Dong-Ming Zhang,焦建伟*
论文出处:
年: 2017
卷:
期: DOI: 10.1093/nar/gkx1295
页:
联系作者: 焦建伟
发表期刊: Nucleic Acids Research
ISSN:
第一作者所在部门:
收录类别:
论文链接: https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkx1295/4780167
影响因子:
摘要: Defects in neurogenesis alter brain circuit formations and may lead to neurodevelopmental disorders such as autism and schizophrenia. Histone H2A.z, a variant of histone H2A, plays critical roles in chromatin structure and epigenetic regulation, but its function and mechanism in brain development remain largely unknown. Here, we find that the deletion of H2A.z results in enhanced proliferation of neural progenitors but reduced neuronal differentiation. In addition, neurons in H2A.z knockout mice exhibit abnormal dendrites during brain development. Furthermore, H2A.zcKO mice exhibit serial behavioral deficits, such as decreased exploratory activity and impaired learning and memory. Mechanistically, H2A.z regulates embryonic neurogenesis by targeting Nkx2–4 through interaction with Setd2, thereby promoting H3K36me3 modification to activate the transcription of Nkx2–4. Furthermore, enforced expression of Nkx2–4 can rescue the defective neurogenesis in the H2A.z-knockdown embryonic brain. Together, our findings implicate the epigenetic regulation by H2A.z in embryonic neurogenesis and provide a framework for understanding how disruption in the H2A.z gene may contribute to neurological disorders.
英文摘要:
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