{"id":1157,"date":"2024-03-05T01:10:59","date_gmt":"2024-03-04T17:10:59","guid":{"rendered":"https:\/\/fanyiming.life\/?p=1157"},"modified":"2025-12-21T01:06:02","modified_gmt":"2025-12-20T17:06:02","slug":"super-enhancer","status":"publish","type":"post","link":"https:\/\/fanyiming.life\/?p=1157","title":{"rendered":"Super enhancer"},"content":{"rendered":"\n

Super enhancer\u7684\u63d0\u51fa\u662f\u4e00\u7bc72013\u5e74Richard Young\u5b9e\u9a8c\u5ba4\u7684Cell\u6587\u7ae0\uff0c\u539f\u6587\u5730\u5740\uff1acell.com\/cell\/pdfExtended\/S0092-8674(13)00392-9<\/a><\/p>\n\n\n\n

Super enhancer\u7684\u5b9a\u4e49\u548c\u7279\u70b9<\/h1>\n\n\n\n

\u5728murine\u80da\u80ce\u5e72\u7ec6\u80de\uff08ESC\uff09\u4e2d\uff0cESC state\u7684\u57fa\u56e0\u8868\u8fbe\u7a0b\u5e8f\u7684\u5efa\u7acb\u6709\u4e24\u4e2a\u5173\u952e\u7684\u8d21\u732e\u8005\u3002<\/p>\n\n\n\n

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\u7b2c\u4e00\u662f\uff0c\u4f9d\u9760\u5c11\u6570\u7684”master transcription factors”\uff0c\u5982Oct4, Sox2, Nanog(OSN)\u7b49\u3002<\/p>\n\n\n\n

\u7b2c\u4e8c\u662f\uff0c\u4f9d\u9760”mediator coactivator complex”\u589e\u5f3a\u7ed3\u5408\u5728enhancer\u4e0a\u7684TFs\u52df\u96c6Pol II\u7684\u80fd\u529b\u3002<\/p>\n<\/blockquote>\n\n\n\n

\u5728\u5b9e\u9a8c\u4e2d\uff0c\u4e0d\u7ba1\u662floss of Oct4\u8fd9\u6837\u7684Master TF\uff0c\u8fd8\u662floss of Mediator\uff0c\u90fd\u80fd\u4f7fESC-specific gene\u7684\u8868\u8fbe\u5feb\u901f\u4e0b\u964d\u3002<\/p>\n\n\n\n

\u6709\u6587\u732e\u8868\u660e\uff0c\u540c\u65f6\u88abOct4, Sox3, Nanog\u4e09\u8005\u7ed3\u5408\u7684DNA\u533a\u57df\u5927\u6982\u7387\u662fenhancer\u3002\u6240\u4ee5\u4f5c\u8005\u6839\u636e\u8fd9\u4e2a\u5728ESC\u4e2d\u9274\u5b9a\u51fa8794\u4e2aenhancer\u3002\u5bf9\u8fd9\u516b\u5343\u591a\u4e2aenhancers\u89c2\u5bdf\uff0c\u4ed6\u4eec\u53d1\u73b0\u8fd9\u4e9benhancer\u5e76\u4e0d\u662f\u5b8c\u5168\u968f\u673a\u7684\u5206\u5e03\u5728\u57fa\u56e0\u7ec4\u4e0a\u7684\uff0c\u5728\u67d0\u4e9b\u533a\u57df\uff0c\u4f1a\u96c6\u4e2d\u51fa\u73b0\u82e5\u5e72\u4e2aenhancers\u5bc6\u96c6\u5806\u79ef\u5728\u4e00\u8d77\uff0c\u5f62\u6210clusters. \u4e00\u822c\u7684enhance\u7684\u957f\u5ea6\u4e5f\u5c31\u51e0\u767e\u4e2a\u78b1\u57fa\u5bf9\uff0c\u800c\u8fd9\u4e9bclusters\u91cc\u7684enhancer\u8fde\u8d77\u6765\u53ef\u4ee5\u957f\u8fbe50kb. \u4e3e\u4e2a\u76f4\u89c2\u7684\u4f8b\u5b50\uff0c\u4e0b\u56fe\u4e0a\u9762\u7684Gck\u91cc\u6700\u5c16\u7684\u90a3\u4e2a\u5cf0\u662f\u4e00\u4e2aenhancer\uff0c\u4e00\u679d\u72ec\u79c0\u3002\u800c\u4e0b\u9762miR-290-295\u9644\u8fd1\u7684enhancer\u8fde\u6210\u4e86clusters\uff0c\u8fde\u7ef5\u4e0d\u7edd\u51e0\u5341kb\u3002<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe1<\/p>\n\n\n\n

\u56e0\u4e3aenhancer\u533a\u57df\u603b\u662f\u5bcc\u96c6\u7740Master TFs\u548cMediator (\u4e0a\u56fe\u7528OSN\u548cMed1\u7684ChIP-seq\u8868\u5f81)\u3002\u6240\u4ee5\u5b83\u4eec\u5c31\u7528Med1\u7684\u4fe1\u53f7\u5f3a\u5ea6\u6765\u5b9a\u4e49\u8fd9\u79cd\u7279\u522b\u957f\u7684enhancer.<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe2<\/p>\n\n\n\n

\u53ef\u4ee5\u770b\u5230\uff0c\u5982\u679c\u628aMed1 signal\u505a\u7d2f\u8ba1\u66f2\u7ebf\uff0c\u7edd\u5927\u591a\u6570\u7684enhancers\u53ea\u6709\u5f88\u5c11\u7684Med1 signal\uff0c\u800c\u6700\u540e\u7684231\u4e2a”enhancer domains”\u5360\u636e\u4e86\u7edd\u5927\u591a\u6570\u7684Med1\uff0c\u8fd9\u79cd231\u4e2a”enhancer domains”\uff0c\u4f5c\u8005\u8d77\u4e86\u4e00\u4e2a\u65b0\u7684\u540d\u5b57\uff0c\u5c31\u53eb”super enhancers”, \u4e0e\u4e4b\u5bf9\u5e94\u7684\u4e0d\u8fd9\u4e48\u957f\u7684\u5c31\u53eb”typical enhancers”.<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe3<\/p>\n\n\n\n

\u4ece\u4e0a\u56fe\u53ef\u4ee5\u76f4\u89c2\u7684\u5bf9\u6bd4typical enhancers\u548csuper enhancers\uff0c\u540e\u8005\u6570\u91cf\u5c11\uff0c\u4f46\u957f\u5ea6\u957f\uff0cMed1\u66f4\u591a\uff0cenhancer\u4e0a\u901a\u5e38\u6709\u7684H3K27ac\u548cH3K4me1\u4e5f\u66f4\u591a\uff0cDNaseI signal\u4e5f\u9ad8\uff0c\u8868\u793a\u67d3\u8272\u8d28\u5f00\u653e\u7a0b\u5ea6\u9ad8\u3002<\/p>\n\n\n\n

\u90a3\u65e2\u7136\u7ecf\u5178\u7684enhancer\u4fe1\u53f7\uff08H3K27ac, H3K4me1, DNase I\uff09\u90fd\u548cMed1\u6709\u7740\u76f8\u540c\u7684\u8d8b\u52bf\uff0c\u90fd\u5728super enhancer\u66f4\u5bcc\u96c6\uff0c\u9664\u4e86\u7528Med1\uff0c\u80fd\u4e0d\u80fd\u4e5f\u7528\u5b83\u4eec\u51e0\u4e2a\u6765\u5b9a\u4e49super enhancers\u5462\uff1f\u4f5c\u8005\u7ed8\u5236\u4e86\u8ddf\u56fe2\u7c7b\u4f3c\u7684\u7d2f\u8ba1\u66f2\u7ebf\uff08\u56fe4\uff09\uff0c\u53d1\u73b0\u867d\u7136\u8d8b\u52bf\u76f8\u540c\uff0c\u4f46\u7528Med1\u662f\u6548\u679c\u6700\u597d\u7684\u3002<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe4<\/p>\n\n\n\n

\u5230\u8fd9\u91cc\uff0c\u4f5c\u8005\u63d0\u51fa\u4e86super enhancer\u8fd9\u4e2a\u6982\u5ff5\uff0c\u4f46\u8bfb\u8005\u81ea\u7136\u4f1a\u60f3\u3002\u8fd9\u6837\u4e00\u4e2a\u6982\u5ff5\u6709\u6ca1\u6709\u63d0\u51fa\u7684\u5fc5\u8981\uff1f\u6709\u6ca1\u6709\u53ef\u80fd\u5c31\u662f\u6070\u597d\u4e00\u5806typical enhancer\u5728\u67d0\u4e9b\u5730\u65b9\u624e\u5806\u5c31\u5f62\u6210\u4e86super enhancer\u5462\uff1f\u5b83\u8ddftypical enhancer\u76f8\u6bd4\uff0c\u9664\u4e86\u66f4\u957f\u4e4b\u5916\uff0c\u6709\u6ca1\u6709\u66f4\u52a0\u72ec\u7279\u7684\u5730\u65b9\u533a\u5206\u5462\uff1f<\/p>\n\n\n\n

\u4e3a\u4e86\u786e\u5b9a\u8fd9\u4e00\u70b9\uff0c\u4f5c\u8005\u505a\u4e86\u4e00\u5927\u5806\u7684ChIP-seq\uff0c\u5305\u62ecTFs, histone modifications, chromatin regulators\u7b49\u7b49\u3002\u6700\u7ec8\u4ed6\u4eec\u53d1\u73b0\uff0c\u6709\u4e24\u4e2aTFs\u786e\u5b9e\u5728typical\u548csuper enhancer\u4e2d\u8868\u73b0\u51fa\u663e\u8457\u5dee\u5f02\uff0c\u5b83\u4eec\u662fKlf4\u548cEsrrb.<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe5<\/p>\n\n\n\n

\u4e0b\u4e00\u6b65\uff0c\u4f5c\u8005\u63a2\u7a76super enhancer\u7684\u5f62\u6210\u539f\u56e0\u3002\u56e0\u4e3aenhancer\u8ddfTFs\u7ed3\u5408\u53d1\u6325\u4f5c\u7528\uff0c\u6240\u4ee5\u81ea\u7136\u60f3\u5230\u6765\u7814\u7a76super enhancer\u4e0a\u6709\u6ca1\u6709\u7279\u5b9a\u7684TFs\u7ed3\u5408motif. \u4ed6\u4eec\u53d1\u73b0\uff0csuper enhancers\u4e0a\u6709Oct4, Sox2, Nanog, Klf4, Esrrb\u7684\u7ed3\u5408motif\uff0c\u4f46\u6ca1\u6709\u5176\u4ed6\u8f6c\u5f55\u56e0\u5b50\u5982CTCF\u548cc-Myc\u7684\u7ed3\u5408motif (\u56fe6)\u3002<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe6<\/p>\n\n\n\n

\u8fdb\u4e00\u6b65\u5bf9\u6bd4typical\u548csuper enhancers\u4e2d\u8fd9\u4e9bmotif\u51fa\u73b0\u7684\u6570\u91cf\uff0c\u53d1\u73b0Oct4, Sox2, Nanog\u7684\u6570\u91cf\u5dee\u4e0d\u591a\uff0c\u800cKlf4\u548cEsrrb\u5728super enhancers\u4e2d\u6709\u66f4\u591a\u7684\u7ed3\u5408motif\uff0c\u8fd9\u89e3\u91ca\u4e86\u4e3a\u4ec0\u4e48\u5728\u56fe5\u4e2d\u89c2\u5bdf\u5230super enhancers\u542b\u6709\u6bd4typical enhancers\u66f4\u591a\u7684Klf4\u548cEsrrb.<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u603b\u7ed3\uff1a<\/p>\n\n\n\n

ESC super-enhancers are large clusters of enhancers<\/strong> that can be distinguished from typical enhancers by the presence of the transcription factors Klf4 and Esrrb<\/strong> and exceptional levels of Mediator<\/strong>. These domains are formed as a consequence of binding of specific master transcription factors<\/strong> to dense clusters of their binding site sequences.<\/p><\/blockquote><\/figure>\n\n\n\n

Super enhancer\u7684\u529f\u80fd<\/h1>\n\n\n\n

enhancer\u7684\u9776\u57fa\u56e0\u901a\u5e38\u5728\u67d3\u8272\u8d28\u4e0a\u4e5f\u4e34\u8fd1enhancers\u672c\u8eab\uff0c\u7528\u8fd9\u4e2a\u539f\u7406\uff0c\u4f5c\u8005\u5bf9ESC\u4e2d\u7684super enhancers\u7684\u9776\u57fa\u56e0\u8fdb\u884c\u7535\u8111\u9884\u6d4b\uff0c\u9274\u5b9a\u5230\u4e00\u6279”super-enhancer-associated genes”\u3002\u5bf9\u8fd9\u4e00\u6279gene list\u8fdb\u884c\u89c2\u5bdf\uff0c\u53d1\u73b0\u5b83\u5305\u542b\u4e86\u51e0\u4e4e\u6240\u6709\u7684\u5bf9ESC\u7ec6\u80de\u547d\u8fd0\u63a7\u5236\u76f8\u5173\u7684\u57fa\u56e0\uff0c\u5176\u4e2d\u5c31\u5305\u62ec\u524d\u9762\u7528\u5230\u7684Oct4, Sox2, Nanog. \u4e0b\u56fe\u662fOct4\u548cSox2\u57fa\u56e0\u5ea7\u4f4d\u4e0a\u7684Nanog\u548cMed1\u7684ChIP profiles\uff0c\u53ef\u4ee5\u53d1\u73b0\u786e\u5b9e\u8ddd\u79bbsuper enhancers\u76f8\u5f53\u8fd1\u3002<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe7<\/p>\n\n\n\n

\u4e3a\u4e86\u8bc1\u660e”super-enhancer-associated genes”\u786e\u5b9e\u53c2\u4e0eESC state\u7684\u8c03\u63a7\uff0c\u4ed6\u4eec\u627e\u4e86\u4e00\u4e2a\u6570\u636e\u96c6\u505aGSEA\uff0c\u53d1\u73b0\u786e\u5b9e\u5bcc\u96c6\u5728\u90a3\u4e9bshRNA knockdown\u540e\u7834\u574fESC state\uff08low Oct4\uff09\u7684\u4e00\u7aef\uff0cGO\u8fd8\u5bcc\u96c6\u5230”Transcription factor activity”\u7684\u6761\u76ee\u3002<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe8<\/p>\n\n\n\n

\u63d0\u51fa\u4e00\u4e2amodel: Oct4, Sox2, Nanog, Klf4, Esrrb\u8fd9\u51e0\u4e2aTFs\u901a\u8fc7\u7ed3\u5408super enhancers\u6b63\u53cd\u9988\u5730\u6fc0\u6d3b\u81ea\u8eab\u7684\u8868\u8fbe\u3002\u540c\u65f6\uff0csuper enhancers\u4e5f\u589e\u5f3a\u5176\u4ed6\u4e0eESC state\u76f8\u5173\u57fa\u56e0\u7684\u8868\u8fbe\u3002<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe9<\/p>\n\n\n\n

\u7edf\u8ba1\u6240\u6709\u57fa\u56e0\uff0c\u53d1\u73b0super enhancers\u786e\u5b9e\u6bd4typical enhancers\u62e5\u6709\u66f4\u5f3a\u7684\u6fc0\u6d3b\u8f6c\u5f55\u7684\u80fd\u529b\uff08\u56fe10\uff09\u3002<\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

\u56fe10<\/p>\n\n\n\n

\u5e76\u4e14\uff0c\u7531\u4e8esuper enhancer\u76f8\u6bd4typical enhancers\u542b\u6709\u66f4\u4e30\u5bcc\u7684TF\u7ed3\u5408\u7684motifs\uff0csuper-enhancer-associated genes\u7684\u57fa\u56e0\u8868\u8fbe\u6c34\u5e73\u53d7Oct4 knockdown\u7684\u5f71\u54cd\u66f4\u663e\u8457\uff08\u56fe11\uff09\u3002<\/p>\n\n\n

\n
\"\"<\/figure>\n<\/div>\n\n\n

\u56fe11<\/p>\n\n\n\n

super enhancer\u540c\u6837\u5b58\u5728\u4e8e\u5df2\u5206\u5316\u7ec6\u80de<\/h1>\n\n\n
\n
\"\"<\/figure>\n<\/div>\n\n\n

\u56fe12<\/p>\n\n\n\n

Super enhancer\u662fcell-specific\u7684<\/h1>\n\n\n
\n
\"\"<\/figure>\n<\/div>\n\n\n

\u56fe13<\/p>\n\n\n\n

Super enhancer\u6807\u8bb0\u5173\u952e\u7684Cell Identity\u57fa\u56e0<\/h1>\n\n\n\n

\u8fd9\u662ftop10 GO\u5bcc\u96c6\u7684biological process\u6761\u76ee<\/p>\n\n\n

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\"\"<\/figure>\n<\/div>\n\n\n

\u56fe14<\/p>\n\n\n\n

\u603b\u7ed3<\/h1>\n\n\n\n

Super enhancer\u7531\u4e00\u7fa4\u5bcc\u96c6master regulator\u548cmediator\u7684enhancers\u7ec4\u6210\uff0c\u62e5\u6709\u66f4\u5f3a\u7684\u589e\u5f3a\u8f6c\u5f55\u80fd\u529b\uff0c\u4e5f\u5bf9TF perturbation\u66f4\u654f\u611f\u3002super enhancers\u662fcell-specific\u7684\uff0c\u4e14\u7279\u5f02\u6027\u5730\u589e\u5f3a\u4e0ecell identity\u76f8\u5173\u57fa\u56e0\u7684\u8868\u8fbe\u3002\u4e0a\u9762\u5b9e\u9a8c\u90fd\u5728\u54fa\u4e73\u52a8\u7269\u4e2d\u505a\u7684\u3002<\/p><\/blockquote><\/figure>\n","protected":false},"excerpt":{"rendered":"

\u8fd9\u7bc7\u7b14\u8bb0\u805a\u7126\u4e8e2013\u5e74Richard Young\u5b9e\u9a8c\u5ba4\u5728\u300aCell\u300b\u4e0a\u63d0\u51fa\u7684\u201c\u8d85\u7ea7\u589e\u5f3a\u5b50\u201d\u6982\u5ff5\u3002\u6587\u7ae0\u4ee5\u5c0f\u9f20\u80da\u80ce\u5e72\u7ec6\u80de\u4e3a\u6a21\u578b\uff0c\u7cfb\u7edf\u9610\u8ff0\u4e86\u8d85\u7ea7\u589e\u5f3a\u5b50\u7684\u5b9a\u4e49\u3001\u533a\u522b\u4e8e\u5178\u578b\u589e\u5f3a\u5b50\u7684\u5173\u952e\u7279\u5f81\uff08\u5982\u5bcc\u96c6Klf4\u3001Esrrb\u53ca\u8d85\u9ad8Mediator\u6c34\u5e73\uff09\uff0c\u53ca\u5176\u5728\u5efa\u7acb\u548c\u7ef4\u6301\u7ec6\u80de\u7279\u5f02\u6027\u57fa\u56e0\u8868\u8fbe\u7a0b\u5e8f\u4e2d\u7684\u6838\u5fc3\u529f\u80fd\u3002<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[],"class_list":["post-1157","post","type-post","status-publish","format-standard","hentry","category-note"],"_links":{"self":[{"href":"https:\/\/fanyiming.life\/index.php?rest_route=\/wp\/v2\/posts\/1157","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/fanyiming.life\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/fanyiming.life\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/fanyiming.life\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/fanyiming.life\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1157"}],"version-history":[{"count":2,"href":"https:\/\/fanyiming.life\/index.php?rest_route=\/wp\/v2\/posts\/1157\/revisions"}],"predecessor-version":[{"id":14123,"href":"https:\/\/fanyiming.life\/index.php?rest_route=\/wp\/v2\/posts\/1157\/revisions\/14123"}],"wp:attachment":[{"href":"https:\/\/fanyiming.life\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1157"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/fanyiming.life\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1157"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/fanyiming.life\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1157"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}