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NAT COMMUN | 夏国良团队王超课题组发现组蛋白去乙酰化酶3(HDAC3)调控卵母细胞成熟分子机制
发布日期:2020-12-17 浏览次数:  信息来源:亚博APP下载链接

 

       xingchengshuhoudecixingburudongwuzaixianchuitifenmidecuxingxianjisudezuoyongxiakeyishixianzhouqixingpailuan,zheishiqifanyuxiayidaidebiyaoqianti。zailuanpaoqi,culuanpaojisu(fsh)cujinluanchaozhongdeluanpaoxunsufayuzhiyouqiangluanpao,cishikelixibaodaliangzengzhidanluanmuxibaoyiranbeizuzhizaidiyicijianshufenlieqianqi(jishengfapaoqi,gvqi);suihouyouyukelixibaozengzhizaochengcijisufenmizengjia,zhengfankuidiaokongcuhuangtijisu(lh)fenmi,chuxianpailuanqianfengzhibingdaozhiluanmuxibaojianshufenliehuifu(shengfapaopolie,gvbd)hepailuan。yiyouyanjiubiaomingfshhelhdoushitongguocunzaiyuluanpaotixibaoshangdemoshoutifahuijingzhundiaokongluanmuxibaojianshufenliezuzhijihuifuzuoyongde。qizhong,lhketongguoyoudaokelixibaobiaodaegfyangshengzhangyinzi(ruareg),jineryoudaoluanqiukuozhanjiluanmuxibaohuifujianshufenlie,danqijutijizhishangbuqingchu。

 

       2019nian12yue16ri,yaboappxiaguoliangtuanduiwangchaoketizuzainature communicationszazhishangfabiaoletiwei“hdac3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the lh surge”deyanjiulunwen。(http://www.nature.com/articles/s41467-019-13671-8)gaiyanjiushoucizhengmingtixibaozhongdebiaoguanyichuanxiushigaibianzailhyoudaoluanmuxibaochengshuhepailuanguochengzhongfahuizheguanjianzuoyong。zuozhefaxianzudanbaiquyixianhuamei3(hdac3)zaikelixibaozhongjiedaolecuxingxianjisuduiluanmuxibaojianshufenliejinchengdediaokong。zailhfengdaolaizhiqian,zhuanluyinzifoxo1dengkejianghdac3mujidaoaregdeqidongziquyu,tongguojiechuzudanbaih3k14deyixianhuaxiushi,zuzhileransezhijiegoukaifangjineryizhilearegdebiaodaheluanmuxibaochengshu。suizhelhfengdechuxian,hdac3deshuipingbeixunsuxiadiao,tongguojiechuqiduiaregqidongziqudeyizhi,jinercujinlezhuanluyinzisp1yuaregqidongziqudejiehedaozhiaregbiaodaxunsuzengjia,luanmuxibaoyincihuifulejianshufenliebingpailuan。gaiyanjiuweichanmingcuxingxianjisuyoudaoluanpaofayuheluanmuxibaochengshudefenzidiaokongjizhitigonglexinzhengju,bingweilinchuangshangyinlhxiangyingshibaizaochengdeluanmuxibaobuchengshuyinqidebuyunzhiliaotigonglexinsilu。

亚博APP       shouxian,gaiyanjiufaxianshengliqingkuangxialuanpaokelixibaozhonghdac3debiaodashuipinghuisuizhelhfengdedaolaichuxianxunsuxiadiao。liyonghdac3kelixibaodeshikongteyiqiaochuxiaoshumoxing,zuozhefaxiandangzailhfengdaolaiqianteyixingqiaochukelixibaozhongdehdac3shi,huidaozhiluanmuxibaotiqianhuifujianshufenlie(tu1)。



       suihou,zuozhefaxiankelixibaozhongbiaodadehdac3ketongguozhijiediaokongaregqidongziqudezudanbaih3k14deyixianhuaxiushi,gaibianqiransezhidekaifangzhuangtaijizhuanluyinzidejiehenengli,jinerzuduanaregdebiaodajiluanmuxibaodejianshufenliehuifujincheng(tu2)。



          zuihou,zuozheliyongtiwaishiyanzhengming,yingyonghdac3deteyixingyizhijikebuyilaiyulhdezuoyongjineryoudaoluanmuxibaotiwaichengshu,qiegaifangfabingbuyingxiangxiaoshuluanmuxibaodefayuqianneng(tu3)。youcizuozherenweihdac3keyizuoweiyigeyouxiaodeyaowubadian,yongyuzaitiwaibuyilaiyucuxingxiansudeqingkuangxiacujinluanmuxibaochengshu。




       总之,该研究首次发现在促性腺素诱导卵母细胞成熟过程中,卵泡颗粒细胞中的组蛋白H3的乙酰化修饰水平改变可作为影响染色体开放状态及相关基因表达的分子开关,进而参与LH诱导卵母细胞成熟排卵的进程。该研究为进一步揭示促性腺激素调控卵母细胞成熟发育的具体分子机制奠定了基础。此外,研究证明可以通过直接干预HDAC3实现不依赖于LH而启动颗粒细胞中AREG的内源性表达,进而以更加符合生理性调节的方式促进卵母细胞体外成熟的目标,这不仅为体外高效低成本地生产家畜卵母细胞用于胚胎工程提供了新思路,也为治疗因患者对LH响应低下进而导致不孕提供了潜在的治疗策略。

       亚博APP博士生王华荣蔡晗王晓为本文的共同第一作者。王超亚博APP副教授为本文的通讯作者。该研究获得了国家重点研发计划项目、科技部“973”项目以及国家自然科学基金等经费的支持。



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