Cell Stem Cell:非经典的BCOR-PRC1.1复合体抑制人胚胎干细胞的分化过程

2018-01-22 MedSci MedSci原创

本研究提高了ESCs中Polycomb靶向和抑制过程理解,并且可以在发育系统中广泛的应用。

Ploycomb group protein在多种干细胞体系中调节自我更新和分化。PCR1和PCR2占据发育基因的启动子,并且作为胚胎干细胞(embryonic stem cells,ESCs)抑制网络的重要组成部分。EZH1/2是 PRC2复合体的催化亚基,甲基化组蛋白H3的Lys27(H3K27me3),而PCR1的RING1/RNF2泛素化H2A的Lys119(H2AK119ub),而这些区域称为Polycomb domain。目前经典模型提出,PRC2通过DNA结合蛋白,例如JARID2,募集于靶位点,从而导致靶位点附近的H3K27me3聚集。而这个标志能够被PRC1复合体的CBX亚基识别。PCR1一旦募集于靶位点就开始聚集H2AK119ub,从而使染色质结构更加紧密,PRC结合区域的基因沉默。

非经典的PRC1复合体在多能性维持过程中也有重要的作用,它保留有RING1/RNF2 E3-泛素化酶,但是有一套独特的附属亚基,并且不依赖对靶位点的H3K27me3修饰。而这些非经典复合体是如何识别并且调节他们的基因靶位点呢?

科学家研究发现BCL6 共抑制因子(BCL co-repressor, BCOR),是PRC1.1复合体的成员,并且在维持人胚胎干细胞原始多能性过程中发挥重要的作用。BCOR减少会导致在关键发育位点和内胚层和中胚层谱系分化起始的Polycomb domain的大幅削减。BCOR的C末端调节组装,并且靶向PRC1.1复合体,然而其N末端参与BCOR-PRC1.1抑制子的功能。

本研究提高了ESCs中Polycomb靶向和抑制过程理解,并且可以在发育系统中广泛的应用。

原文出处:Wang Z, Gearhart M D, Lee Y W, et al. A Non-canonical BCOR-PRC1. 1 Complex Represses Differentiation Programs in Human ESCs[J]. Cell Stem Cell, 2018.DOI: 10.1016/j.stem.2017.12.002

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GetPortalCommentsPageByObjectIdResponse(id=281067, encodeId=f6b428106ec8, content=henhao, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Mon Jan 22 21:47:33 CST 2018, time=2018-01-22, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1950289, encodeId=b2fe19502893d, content=<a href='/topic/show?id=eb4532805e' target=_blank style='color:#2F92EE;'>#Bcor#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3280, encryptionId=eb4532805e, topicName=Bcor)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Sep 15 09:24:00 CST 2018, time=2018-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870406, encodeId=2b6a18e040669, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42601, encryptionId=ca28426010b, topicName=复合体)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=395f25, createdName=bioon1, createdTime=Mon Jul 09 14:24:00 CST 2018, time=2018-07-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1315376, encodeId=078213153e6c7, content=<a href='/topic/show?id=6fcc83e0554' target=_blank style='color:#2F92EE;'>#胚胎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83705, encryptionId=6fcc83e0554, topicName=胚胎)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6393434, createdName=ailian1202, createdTime=Wed Jan 24 07:24:00 CST 2018, time=2018-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1351231, encodeId=c703135123166, content=<a href='/topic/show?id=37b083e182b' target=_blank style='color:#2F92EE;'>#胚胎干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83718, encryptionId=37b083e182b, topicName=胚胎干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jan 24 07:24:00 CST 2018, time=2018-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482071, encodeId=793114820e1a9, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Wed Jan 24 07:24:00 CST 2018, time=2018-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=281067, encodeId=f6b428106ec8, content=henhao, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Mon Jan 22 21:47:33 CST 2018, time=2018-01-22, status=1, ipAttribution=)]
    2018-12-07 维他命
  6. [GetPortalCommentsPageByObjectIdResponse(id=1950289, encodeId=b2fe19502893d, content=<a href='/topic/show?id=eb4532805e' target=_blank style='color:#2F92EE;'>#Bcor#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3280, encryptionId=eb4532805e, topicName=Bcor)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Sep 15 09:24:00 CST 2018, time=2018-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1870406, encodeId=2b6a18e040669, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, 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target=_blank style='color:#2F92EE;'>#胚胎干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83718, encryptionId=37b083e182b, topicName=胚胎干细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jan 24 07:24:00 CST 2018, time=2018-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482071, encodeId=793114820e1a9, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Wed Jan 24 07:24:00 CST 2018, time=2018-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=281067, encodeId=f6b428106ec8, content=henhao, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NcXNhUvfhzd2VdicMnaLeK2Im5gKx4Ucxd8Bwu6S7RG0uILBFQx5HTW2bU4VricDYlQqN20ibASSMYAeGrZrrTpy2Q/0, createdBy=b0041939716, createdName=hhh678, createdTime=Mon Jan 22 21:47:33 CST 2018, time=2018-01-22, status=1, ipAttribution=)]
    2018-07-09 bioon1
  7. 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    2018-01-24 ailian1202
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    2018-01-22 hhh678

    henhao

    0

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研究人员开发了一种新型双色TaqMan探针实时PCR方法,可同时在12个平行反应中筛选45个融合转录本。该方法用携带已知融合转录物和患者样品的细胞系进行测试和验证。