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ELife:北京大学何爱彬研究组等发现PRC2-EED与HDACs控制基因转录抑制程序的新机制

2017-04-17 佚名 生物帮

2017年4月10日,国际知名期刊《eLife》杂志在线发表了北京大学分子医学研究所何爱彬研究组和美国哈佛医学院波士顿儿童医院William T. Pu教授共同合作的题为“ EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent”的研究论文。研究回答了组蛋白修饰H3K2

2017年4月10日,国际知名期刊《eLife》杂志在线发表了北京大学分子医学研究所何爱彬研究组和美国哈佛医学院波士顿儿童医院William T. Pu教授共同合作的题为“ EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent”的研究论文。研究回答了组蛋白修饰H3K27me3还是其修饰酶PRC2本身发挥抑制基因转录的直接作用这一关键科学问题,揭示表观图谱与心脏发育异常能通过操控表观遗传修饰酶的遗传互作得以修复。北京大学分子医学研究所博士生艾珊珊和彭勇为本文的共同第一作者。分何爱彬研究员以及William T. Pu教授为本文的共同通讯作者。

PRC2 (Ploycomb Repressive Complex2) 是一个重要的表观遗传修饰酶复合体,一般认为它能催化H3K27me3(抑制性组蛋白修饰)的形成从而抑制基因表达,但是到底PRC2还是H3K27me3是抑制基因表达的根本因素仍然未知。前期所有对该机制的研究都集中在高增殖的胚胎干细胞或其他增殖活跃的细胞或组织中,H3K27me3重新合成为表观遗传密码正确传递给子代所必须,但同时也导致不能区分哪一个是抑制基因表达的直接因素。成体心脏的心肌细胞处于不增殖状态,无需增殖相关的组蛋白修饰的干扰,为研究该机制提供了极好的条件。研究发现在心肌细胞中特异敲除EED(PRC2的核心蛋白)导致了扩张型心肌病的发生,表达上升(去阻遏)的大部分基因其H3K27me3修饰水平并没有下降,H3K27ac(一种处于激活状态的组蛋白标记)的修饰水平伴随着升高。通过一系列的遗传rescue实验,发现了EED与组蛋白去乙酰化酶HDACs的遗传与生化互作,表观图谱与基因表达的失调导致的发育异常可以通过纠正H3K27ac的修饰图谱得以恢复,而不依赖于H3K27me3的修饰。因此,该研究表明EED作为染色质remodeler起着发挥抑制基因转录的关键作用,H3K27me3可能是基因转录抑制的伴随结果,证明了表观调控异常导致的基因表达失调可以被表观遗传图谱的重新改写而得到恢复,这为先天性心脏病和其他疾病的治疗提供了理论依据。



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    2017-06-08 mjldent
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    2017-05-16 clmlylxy
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    2017-10-11 膀胱癌
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    2017-11-08 zhishijing
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    2017-08-13 lingaifan
  7. [GetPortalCommentsPageByObjectIdResponse(id=1747232, encodeId=07fd1e4723277, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Thu Jun 08 00:04:00 CST 2017, time=2017-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776342, encodeId=df371e7634250, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Dec 02 18:04:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2068496, encodeId=9691206849667, content=<a href='/topic/show?id=59371088215' target=_blank style='color:#2F92EE;'>#Life#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10882, encryptionId=59371088215, topicName=Life)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Tue May 16 18:04:00 CST 2017, time=2017-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1972995, encodeId=b52019e29956c, content=<a href='/topic/show?id=72d566e3a6' target=_blank style='color:#2F92EE;'>#eLife#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6673, encryptionId=72d566e3a6, topicName=eLife)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Wed Oct 11 19:04:00 CST 2017, time=2017-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702893, encodeId=37791e0289372, content=<a href='/topic/show?id=c9e21461892' target=_blank style='color:#2F92EE;'>#PRC2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14618, encryptionId=c9e21461892, topicName=PRC2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cdb330453655, createdName=zhishijing, createdTime=Wed Nov 08 19:04:00 CST 2017, time=2017-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2003405, encodeId=64152003405b7, content=<a href='/topic/show?id=86d585931d' target=_blank style='color:#2F92EE;'>#HDAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8593, encryptionId=86d585931d, topicName=HDAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Aug 13 04:04:00 CST 2017, time=2017-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1279158, encodeId=374612e9158ca, content=<a href='/topic/show?id=316d1882bc' target=_blank style='color:#2F92EE;'>#ACS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1882, encryptionId=316d1882bc, topicName=ACS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Wed Apr 19 10:04:00 CST 2017, time=2017-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=188288, encodeId=fab91882887a, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=129, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Mon Apr 17 19:28:25 CST 2017, time=2017-04-17, status=1, ipAttribution=)]
    2017-04-19 yaanren
  8. [GetPortalCommentsPageByObjectIdResponse(id=1747232, encodeId=07fd1e4723277, content=<a href='/topic/show?id=832e93345c3' target=_blank style='color:#2F92EE;'>#转录#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93345, encryptionId=832e93345c3, topicName=转录)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=58df35929710, createdName=mjldent, createdTime=Thu Jun 08 00:04:00 CST 2017, time=2017-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1776342, encodeId=df371e7634250, content=<a href='/topic/show?id=7d9d33646c8' target=_blank style='color:#2F92EE;'>#北京大学#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33646, encryptionId=7d9d33646c8, topicName=北京大学)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f6cc38925383, createdName=lixiaol, createdTime=Sat Dec 02 18:04:00 CST 2017, time=2017-12-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2068496, encodeId=9691206849667, content=<a href='/topic/show?id=59371088215' target=_blank style='color:#2F92EE;'>#Life#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10882, encryptionId=59371088215, topicName=Life)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc8528, createdName=clmlylxy, createdTime=Tue May 16 18:04:00 CST 2017, time=2017-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1972995, encodeId=b52019e29956c, content=<a href='/topic/show?id=72d566e3a6' target=_blank style='color:#2F92EE;'>#eLife#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6673, encryptionId=72d566e3a6, topicName=eLife)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Wed Oct 11 19:04:00 CST 2017, time=2017-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702893, encodeId=37791e0289372, content=<a href='/topic/show?id=c9e21461892' target=_blank style='color:#2F92EE;'>#PRC2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14618, encryptionId=c9e21461892, topicName=PRC2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cdb330453655, createdName=zhishijing, createdTime=Wed Nov 08 19:04:00 CST 2017, time=2017-11-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2003405, encodeId=64152003405b7, content=<a href='/topic/show?id=86d585931d' target=_blank style='color:#2F92EE;'>#HDAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8593, encryptionId=86d585931d, topicName=HDAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Aug 13 04:04:00 CST 2017, time=2017-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1279158, encodeId=374612e9158ca, content=<a href='/topic/show?id=316d1882bc' target=_blank style='color:#2F92EE;'>#ACS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1882, encryptionId=316d1882bc, topicName=ACS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=102a153, createdName=yaanren, createdTime=Wed Apr 19 10:04:00 CST 2017, time=2017-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=188288, encodeId=fab91882887a, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=129, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Mon Apr 17 19:28:25 CST 2017, time=2017-04-17, status=1, ipAttribution=)]
    2017-04-17 三生有幸9135

    学习一下谢谢分享

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