维甲酸诱导小鼠神经管畸形胚脑中H2BK120ub1的全基因组状态变化  

Genome-wide changes of H2BK120ub1 inmouse neural tube defect embryos induced by retinoic acid

作　　者：王珊[1] 何学佳 成翕悦 林烨[1] 裴培[1] 占小俊 WANG Shan;HE Xue-jia;CHENG Xi-yue;LIN Ye;PEI Pei;ZHAN Xiao-jun(Beijing Municipal Key Laboratory of Child Development and Nutriomics,Capital Institute of Pediatrics,Beijing 100020,China;不详)

机构地区：[1]首都儿科研究所北京市儿童发育与营养学重点实验室,北京100020 [2]北京大学首都儿科研究所教学医院 [3]河北医科大学第三医院

出　　处：《中国儿童保健杂志》2022年第7期731-736,共6页Chinese Journal of Child Health Care

基　　金：国家自然基金面上项目(82071690);首都儿科研究所所级基金(FX-2020-05,CXYJ-2-21-09);北京市医管中心“使命”人才培养计划项目-耳鼻咽喉科学(SML20190601)。

摘　　要：目的 利用染色质免疫共沉淀测序技术(ChIP-seq)分析E10.5 d正常小鼠胚脑组织与维甲酸(RA)诱导神经管缺陷(NTDs)小鼠胚脑组织H2BK120单泛素化(H2BK120ub1)修饰的全基因图谱,以期发现H2BK120ub1修饰与神经管发育通路基因表达的关系,为NTDs的诊断及治疗提供生物学靶点及依据。方法 孕鼠分为随机对照组和RA诱导的NTDs组,利用ChIP-seq技术对获得的H2BK120ub1特异结合DNA片段进行序列鉴定,获取比对Reads,进行全基因组的Peak分析、基因注释(GO)以及功能富集分析peak相关基因的生物学功能。结果 E10.5 d正常小鼠脑组织和RA诱导神经管畸形小鼠脑组织两组间有306个基因有显著的H2BK120ub1差异,根据GO富集的基因个数进行统计:在cellular component中前三位为别为Cell(82个基因), Cell part(82个基因),Organelle part(52个基因);在biological process中前三位为别为celluar process(68个基因),metabolic process(47个基因),biological regulation(40个基因);KEGG通路分析的结果主要富集于刺猬因子(HH)信号通路、TGF-beta信号通路、Wnt信号通路等参与调控神经管发育的关键信号通路,有显著统计学意义(P<0.05)。结论 H2BK120ub1修饰的差异可作为NTDs的一个潜在的诊断及治疗靶点。Objective To analyze the difference in genome-wide profile of H2BK120 monoubiquitination(H2BK120ub1) modification in embryonic brain tissue between E10.5 day normal mice and mice with retinoic acid(RA)-induced neural tube defects(NTDs) by chromatin immunoprecipitation sequencing(ChIP-seq), and to explore the relationship between H2BK120ub1 modification and gene expression in the neural tube development pathway, so as to provide a biological target for the diagnosis and treatment of NTDs. Methods The pregnant mice were randomly divided into control group and RA-induced NTDs group. DNA of samples was extracted by ChIP-seq. The compared reads were obtained, then peak analysis of whole genome, GO enrichment analysis of the biological functions of the related peak genes were conducted. Results Totally 306 genes displayed significant H2BK120ub1 differences between control group and NTDs group. The top three genes in the cellular component were Cell(82 genes), Cell part(82 genes), and Organelle part(52 genes). The top three genes in the biological process were celluar process(68 genes), metabolic process(47 genes) and biological regulation(40 genes). The results of KEGG pathway analysis were mainly enriched in differential genes involved in key signaling pathways that regulate long plate chondro-genesis such as hedgehog factor(HH) signaling pathway, TGF-beta signaling pathway and Wnt signaling pathway(P<0.05). Conclusion H2BK120ub1 may be a potential biomarker or a promising target for epigenetic-based NTDs disease treatment.

关 键 词：维甲酸 H2BK120ub 神经管缺陷 染色质免疫共沉淀测序技术 

分 类 号：R748[医药卫生—神经病学与精神病学]