Genes & Devel:组蛋白修饰的特殊标记或是开发长寿疗法的新型靶点

2015-04-20 佚名 生物谷

对DNA缠绕的修饰蛋白进行研究或可帮助阐明线虫、果蝇等生物基因调节和老化及长寿的关系,同时也可以为开发治疗年龄相关疾病的新型靶向药物提供希望。近日,一篇发表于国际杂志Genes and Development上的研究论文中,来自康奈尔大学的研究人员发表了其对组蛋白H3进行特殊修饰的研究。如果说组蛋白就是线轴,那么DNA就是缠绕在线轴上螺线;组蛋白对于包装细胞内的DNA非常必要,而其也可以被以多种方

对DNA缠绕的修饰蛋白进行研究或可帮助阐明线虫、果蝇等生物基因调节和老化及长寿的关系,同时也可以为开发治疗年龄相关疾病的新型靶向药物提供希望。近日,一篇发表于国际杂志Genes and Development上的研究论文中,来自康奈尔大学的研究人员发表了其对组蛋白H3进行特殊修饰的研究。

如果说组蛋白就是线轴,那么DNA就是缠绕在线轴上螺线;组蛋白对于包装细胞内的DNA非常必要,而其也可以被以多种方式所修饰,这些方式都可以影响DNA的包装形式以及基因的开启与关闭。名为H3K36me3的H3组蛋白的修饰指的是在H3蛋白的特殊位点上进行化学标记。

研究者Sylvia Lee表示,我们描述了H3修饰的全基因组模式,随后描述了年幼和年长的秀丽隐杆线虫机体所有基因的表达,结果发现当基因(DNA)缠绕在H3上时,如果H3的修饰水平较低,那么基因的表达就趋向于随着年龄增长而发生波动,同时如果H3处于高水平修饰的状态,那么基因的表达就会随着年龄增长而保持稳定的状态。

如果组蛋白的标记是在高水平时被发现的,那么其就可以在整个机体老化阶段稳定基因的表达;那么是否对秀丽隐杆线虫的这种特殊模式也可以在其它物种中观察到呢?研究人员联合布朗大学的研究者共同研究,对黑腹果蝇进行了相关的检测,发现该模式在黑腹果蝇中也存在。那么研究者就有理由相信这种模式或许在人类机体中也会存在。

随后研究者在秀丽隐杆线虫机体中剔除了促进H3蛋白发生化学标记的酶类,以便这种修饰不会存在,在没有该化学标记存在时,随着年龄进展基因表达就会不断发生变化,而且线虫的寿命也会缩短。于是研究者就推测组蛋白的标记或许对于维持机体正常长寿非常关键;下一步他们就推测,在线虫和果蝇机体中发现的结论是否在哺乳动物和人类中也存在呢?尽管在包括人类细胞在内的不同细胞中存在H3蛋白的修饰,但是研究者对于这种修饰的功能却知之甚少。

研究者Lee最后表示,从临床角度来讲,H3K36me3修饰和许多缺失性发育及癌症发展有关,而识别组蛋白修饰及疾病发展结果的蛋白配偶体或许是后期开发治疗疾病的新型靶点。

原始出处:

Mintie Pu1, Zhuoyu Ni1, Minghui Wang2, Xiujuan Wang1,3, Jason G. Wood4, Stephen L. Helfand4, Haiyuan Yu3 and Siu Sylvia Lee1.Trimethylation of Lys36 on H3 restricts gene expression change during aging and impacts life span.Genes & Dev.April 15, 2015, 29(8): 718-731.doi:10.1101/gad.254144.114

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    2016-01-06 fzwish20000
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    2016-02-09 cy0324
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    2015-04-22 xqptu
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    2015-04-22 zhangyxzsh
  6. [GetPortalCommentsPageByObjectIdResponse(id=1982219, encodeId=f40f1982219bb, content=<a href='/topic/show?id=13b658e849' target=_blank style='color:#2F92EE;'>#Dev#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5878, encryptionId=13b658e849, topicName=Dev)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bcaa382, createdName=fzwish20000, createdTime=Wed Jan 06 10:14:00 CST 2016, time=2016-01-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048655, encodeId=da35204865522, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Tue Feb 09 11:14:00 CST 2016, time=2016-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1664729, encodeId=9ce11664e29a5, content=<a href='/topic/show?id=81bfe77426a' target=_blank style='color:#2F92EE;'>#组蛋白修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77742, encryptionId=81bfe77426a, topicName=组蛋白修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b8aa25820406, createdName=12498cb5m21暂无昵称, createdTime=Wed Nov 04 17:14:00 CST 2015, time=2015-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384648, encodeId=4f0e13846480b, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Wed Apr 22 06:14:00 CST 2015, time=2015-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569264, encodeId=c3fa15692641e, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Wed Apr 22 06:14:00 CST 2015, time=2015-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=21470, encodeId=028d214e03f, content=长寿另一面就是肿瘤, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=58.33.140.**, createdTime=Mon Apr 20 21:20:00 CST 2015, time=2015-04-20, status=1, ipAttribution=)]
    2015-04-20 58.33.140.**

    长寿另一面就是肿瘤

    0