J Hematol Oncol：BRD4抑制RhoB转录，促进终末红细胞生成

21小时前吾乃喵大人 MedSci原创发表于上海

研究揭示BRD4调控细胞增殖的作用则依赖于其与CDK9的经典复合物结合。这一发现不仅丰富了BRD4的功能认知，也为体外血细胞生成及相关疾病的治疗提供了新靶点。

研究亮点报告发现，表观遗传调控因子BRD4通过抑制RhoB的表达，负向调控人类红细胞终末分化过程。 BRD4促进细胞增殖的经典机制依赖于其CDK9结合功能，而促进红细胞成熟则独立于CDK9，揭示了BRD4的非典型转录抑制功能。阻断BRD4与组蛋白甲基转移酶EHMT1/2的相互作用解除对RhoB的转录抑制，继而通过调控肌动蛋白重组促进红细胞终末分化和核排出。红细胞的产生始于造血干/祖细胞（HSCs），经历早期分化、终末分化以及网织红细胞成熟。终末红细胞生成过程中，细胞经历从原红细胞到幼稚红细胞、基底性红细胞、多染性红细胞以及正染性红细胞的连续分化阶段，同时伴有DNA染色质浓缩、细胞及细胞核体积缩小、血红蛋白合成以及膜蛋白重组。精准的转录因子、共激活因子与染色质重塑因子协同，确保红细胞特异性基因的表达正确调控。异常可引发如骨髓增生异常综合征（MDS）、钻石黑芬贫血等病理状态。目前，尽管对于参与终末红细胞分化的转录及表观遗传调控因子已有若干研究，但关键调控因子体系及其作用机制尚不完善。特别，BET家族蛋白中BRD4以其经典结合CDK9促进RNA聚合酶II延伸的激活作用闻名，但其在红细胞

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472eaeddb605667d2cd9478790a05e1b_5e1756aefc98da4d510babfcfe752deb_8.pdf

你可能还想了解：

EHMT1/2抑制剂是否能够模拟BRD4抑制剂的促红细胞分化作用？

BRD4在红细胞分化中的双重功能(增殖促进vs分化促进)如何影响贫血治疗策略的设计？

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4小时前 屋顶瞄爱赏月来自贵州省

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7小时前 135672_1610 来自山东省

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14小时前 ms4000001513304915 来自广东省

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[GetPortalCommentsPageByObjectIdResponse(id=2274885, encodeId=b2d322e48858b, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Jul 26 09:47:37 CST 2025, time=4小时前, status=0, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2274865, encodeId=ad9022e4865fb, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb026286625, createdName=135672_1610, createdTime=Sat Jul 26 06:18:53 CST 2025, time=7小时前, status=0, ipAttribution=山东省), GetPortalCommentsPageByObjectIdResponse(id=2274857, encodeId=519122e485775, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1646442901, createdName=ms4000001513304915, createdTime=Fri Jul 25 23:51:05 CST 2025, time=14小时前, status=0, ipAttribution=广东省), GetPortalCommentsPageByObjectIdResponse(id=2274847, encodeId=3c7122e48472d, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Fri Jul 25 22:37:48 CST 2025, time=15小时前, status=0, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2274842, encodeId=2b1322e4842a5, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Fri Jul 25 20:22:52 CST 2025, time=17小时前, status=0, ipAttribution=山西省), GetPortalCommentsPageByObjectIdResponse(id=2274839, encodeId=7cba22e48391a, content=<a href='/topic/show?id=9fd33e0829' target=_blank style='color:#2F92EE;'>#BRD4#</a> <a href='/topic/show?id=1aed12832ec8' target=_blank style='color:#2F92EE;'>#终末红细胞生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=3, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3708, encryptionId=9fd33e0829, topicName=BRD4), TopicDto(id=128327, encryptionId=1aed12832ec8, topicName=终末红细胞生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cade5395722, createdName=梅斯管理员, createdTime=Fri Jul 25 17:05:24 CST 2025, time=21小时前, status=1, ipAttribution=上海)]
15小时前 1209e435m98(暂无昵称) 来自浙江省

前往app查看评论内容

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[GetPortalCommentsPageByObjectIdResponse(id=2274885, encodeId=b2d322e48858b, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Jul 26 09:47:37 CST 2025, time=4小时前, status=0, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2274865, encodeId=ad9022e4865fb, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb026286625, createdName=135672_1610, createdTime=Sat Jul 26 06:18:53 CST 2025, time=7小时前, status=0, ipAttribution=山东省), GetPortalCommentsPageByObjectIdResponse(id=2274857, encodeId=519122e485775, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1646442901, createdName=ms4000001513304915, createdTime=Fri Jul 25 23:51:05 CST 2025, time=14小时前, status=0, ipAttribution=广东省), GetPortalCommentsPageByObjectIdResponse(id=2274847, encodeId=3c7122e48472d, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Fri Jul 25 22:37:48 CST 2025, time=15小时前, status=0, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2274842, encodeId=2b1322e4842a5, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Fri Jul 25 20:22:52 CST 2025, time=17小时前, status=0, ipAttribution=山西省), GetPortalCommentsPageByObjectIdResponse(id=2274839, encodeId=7cba22e48391a, content=<a href='/topic/show?id=9fd33e0829' target=_blank style='color:#2F92EE;'>#BRD4#</a> <a href='/topic/show?id=1aed12832ec8' target=_blank style='color:#2F92EE;'>#终末红细胞生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=3, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3708, encryptionId=9fd33e0829, topicName=BRD4), TopicDto(id=128327, encryptionId=1aed12832ec8, topicName=终末红细胞生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cade5395722, createdName=梅斯管理员, createdTime=Fri Jul 25 17:05:24 CST 2025, time=21小时前, status=1, ipAttribution=上海)]
17小时前 医鸣惊人来自山西省

前往app查看评论内容

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[GetPortalCommentsPageByObjectIdResponse(id=2274885, encodeId=b2d322e48858b, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211111/81c0b64745c644319545ec26d7ef0b34/9ddb2864d5df4dd9bf4305e380bffc96.jpg, createdBy=c7835705079, createdName=屋顶瞄爱赏月, createdTime=Sat Jul 26 09:47:37 CST 2025, time=4小时前, status=0, ipAttribution=贵州省), GetPortalCommentsPageByObjectIdResponse(id=2274865, encodeId=ad9022e4865fb, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb026286625, createdName=135672_1610, createdTime=Sat Jul 26 06:18:53 CST 2025, time=7小时前, status=0, ipAttribution=山东省), GetPortalCommentsPageByObjectIdResponse(id=2274857, encodeId=519122e485775, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a1646442901, createdName=ms4000001513304915, createdTime=Fri Jul 25 23:51:05 CST 2025, time=14小时前, status=0, ipAttribution=广东省), GetPortalCommentsPageByObjectIdResponse(id=2274847, encodeId=3c7122e48472d, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Fri Jul 25 22:37:48 CST 2025, time=15小时前, status=0, ipAttribution=浙江省), GetPortalCommentsPageByObjectIdResponse(id=2274842, encodeId=2b1322e4842a5, content=前往app查看评论内容, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Fri Jul 25 20:22:52 CST 2025, time=17小时前, status=0, ipAttribution=山西省), GetPortalCommentsPageByObjectIdResponse(id=2274839, encodeId=7cba22e48391a, content=<a href='/topic/show?id=9fd33e0829' target=_blank style='color:#2F92EE;'>#BRD4#</a> <a href='/topic/show?id=1aed12832ec8' target=_blank style='color:#2F92EE;'>#终末红细胞生成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=3, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3708, encryptionId=9fd33e0829, topicName=BRD4), TopicDto(id=128327, encryptionId=1aed12832ec8, topicName=终末红细胞生成)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cade5395722, createdName=梅斯管理员, createdTime=Fri Jul 25 17:05:24 CST 2025, time=21小时前, status=1, ipAttribution=上海)]
21小时前 梅斯管理员来自上海

#BRD4# #终末红细胞生成#

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