{"id":62151,"date":"2015-03-24T00:24:21","date_gmt":"2015-03-23T16:24:21","guid":{"rendered":"http:\/\/highscope.ch.ntu.edu.tw\/wordpress\/?p=62151"},"modified":"2021-10-06T16:11:43","modified_gmt":"2021-10-06T08:11:43","slug":"%e6%9f%93%e8%89%b2%e9%ab%94%e7%b5%90%e6%a7%8b%e6%8d%95%e6%8d%89%e6%8a%80%e8%a1%93","status":"publish","type":"post","link":"http:\/\/localhost\/%e6%9f%93%e8%89%b2%e9%ab%94%e7%b5%90%e6%a7%8b%e6%8d%95%e6%8d%89%e6%8a%80%e8%a1%93\/","title":{"rendered":"\u67d3\u8272\u9ad4\u7d50\u69cb\u6355\u6349\u6280\u8853"},"content":{"rendered":"

\u67d3\u8272\u9ad4\u7d50\u69cb\u6355\u6349\u6280\u8853 (3C, Chromosome Conformation Capture)<\/strong><\/span>
\n\u570b\u7acb\u81fa\u7063\u5927\u5b78\u52d5\u7269\u6240\u78a9\u58eb\u9673\u653f\u5100<\/strong><\/span><\/p>\n

\u81ea\u5f9e\u4eba\u985e\u958b\u59cb\u4f7f\u7528\u986f\u5fae\u93e1\u89c0\u5bdf\u7d30\u80de\u4ee5\u4f86\uff0c\u7d30\u80de\u6838\u5167\u7684\u7d72\u72c0\u67d3\u8272\u9ad4\u69cb\u9020\u4e00\u76f4\u70ba\u79d1\u5b78\u5bb6\u6240\u597d\u5947\u3002\u96a8\u8457\u9010\u6b65\u5efa\u69cb\u7684\u907a\u50b3\u5b78\u8207\u751f\u7269\u5316\u5b78\u6982\u5ff5\uff0c\u5305\u62ec\uff1a\u7531\u56db\u500b\u9e7c\u57fa\u69cb\u6210\u5bc6\u78bc\u7684DNA\u662f\u751f\u7269\u9ad4\u5167\u7684\u4e3b\u8981\u907a\u50b3\u7269\u8cea\uff0c\u5f71\u97ff\u6027\u72c0\u8868\u73fe\u7684\u57fa\u56e0\u4f4d\u5728\u67d3\u8272\u9ad4\u4e0a\uff0cDNA\u662f\u7531\u96d9\u80a1\u87ba\u65cb\u5206\u5b50\u6240\u69cb\u6210\uff0c\u5f37\u5316\u5b50 (enhancer) \u5f71\u97ff\u555f\u52d5\u5b50 (promoter) \u5c0d\u5176\u6240\u5c6c\u57fa\u56e0\u7684\u8868\u73fe\u8abf\u63a7\u7b49\u3002<\/p>\n

\u73fe\u4eca\u751f\u7269\u5b78\u5bb6\u666e\u904d\u8a8d\u70ba\u7d30\u80de\u6838\u5167\u7684DNA\u69cb\u9020\uff0c\u9664\u4e86\u7d30\u80de\u8907\u88fd\u6642\u7dca\u5bc6\u5806\u758a\u7684\u67d3\u8272\u9ad4\u7d50\u69cb\u4ee5\u5916\uff0c\u67d3\u8272\u9ad4\u5e8f\u5217\u4e4b\u9593\u7684\u4ea4\u4e92\u4f5c\u7528\u6240\u7522\u751f\u7684\u67d3\u8272\u9ad4\u69cb\u9020\uff0c\u53ef\u80fd\u5c0d\u7d30\u80de\u9593\u671f\u7684\u57fa\u56e0\u8868\u73fe\u7522\u751f\u5f71\u97ff\u3002\u85c9\u7531\u67d3\u8272\u9ad4\u87a2\u5149\u539f\u4f4d\u96dc\u4ea4 (fluorescent chromosome in situ<\/i> hybridization)\uff0c\u5e8f\u5217\u4e4b\u9593\u7684\u4ea4\u4e92\u4f5c\u7528\u53ef\u4ee5\u76f4\u63a5\u7528\u986f\u5fae\u93e1\u89c0\u5bdf\u3002\u53e6\u5916\u4f7f\u7528\u751f\u7269\u5316\u5b78\u65b9\u6cd5\u5254\u9664\u57fa\u56e0\u9ad4\u5167\u7279\u5b9aDNA\u7247\u6bb5\uff0c\u63a5\u8457\u6e2c\u5b9a\u53ef\u80fd\u7684\u76ee\u6a19\u57fa\u56e0\u8868\u73fe\uff0c\u4e5f\u80fd\u63a8\u6e2c\u5e8f\u5217\u9593\u662f\u5426\u6709\u540c\u4f4d\u8abf\u63a7 (cis<\/i>-regulation)\u3002<\/p>\n

\u7136\u800c\uff0c\u4e0a\u8ff0\u6280\u8853\u5728\u4e00\u500b\u7814\u7a76\u8a08\u5283\u4e2d\uff0c\u50c5\u80fd\u63a2\u8a0e\u4e00\u500b\u6216\u6578\u500b\u7247\u6bb5\u7684\u53ef\u80fd\u529f\u80fd\uff0c\u4e14\u53d7\u9650\u65bc\u986f\u5fae\u93e1\u7684\u89e3\u6790\u5ea6\uff0c\u5c0d\u65bc\u7814\u7a76\u64c1\u6709\u6578\u767e\u842c\u9e7c\u57fa\u5c0d\u7684\u771f\u6838\u751f\u7269\u7d30\u80de\u57fa\u56e0\u8abf\u63a7\u6a21\u7d44\uff0c\u4ecd\u9700\u8981\u6295\u5165\u76f8\u7576\u5927\u7684\u8cc7\u6e90\u8207\u6642\u9593\u3002<\/p>\n

\u57282002\u5e74\uff0c\u7f8e\u570b\u54c8\u4f5b\u5927\u5b78Dekker\u535a\u58eb\u6240\u9818\u5c0e\u7684\u5718\u968a\u65bc\u79d1\u5b78 (Science) \u671f\u520a\u767c\u8868\u67d3\u8272\u9ad4\u7d50\u69cb\u6355\u6349\u6280\u8853 (Chromosome Conformation Capture, 3C) \u6280\u8853 (Dekker et al., 2002)\uff0c\u5c07\u7d30\u80de\u6838\u5167DNA\u5e8f\u5217\u65bc\u7a7a\u9593\u4e0a\u7684\u4ea4\u4e92\u4f5c\u7528\u95dc\u4fc2\u4ee5\u66f4\u70ba\u7cbe\u78ba\u7684\u65b9\u5f0f\u89e3\u69cb\u4e26\u5448\u73fe\u3002<\/p>\n

\"32101\"<\/a>

\u5716\u4e00 3C\u6280\u8853\u539f\u7406\u8207\u884d\u751f\u4e4b4C\u30015C\u53caHi-C\u6280\u8853\u3002\uff08\u672c\u6587\u4f5c\u8005\u9673\u653f\u5100\u7e6a\uff09<\/p><\/div>\n

\u4ed6\u5011\u7684\u5be6\u9a57\u9996\u5148\u4f7f\u7528\u4f4e\u6fc3\u5ea6\u798f\u99ac\u6797 (formaldehyde) \u8655\u7406\u7d30\u80de\uff0c\u4f7f\u8ddd\u96e2\u76f8\u8fd1\u7684\u7d72\u72c0\u67d3\u8272\u9ad4 (DNA) \u7522\u751f\u9375\u7d50 (cross-linking)\uff0c\u518d\u7528\u9650\u5236\u9176 (restriction enzyme) \u5c07\u5927\u7247\u6bb5DNA\u5207\u6210\u5c0f\u7247\u6bb5\uff0c\u4f7f\u5f97\u9375\u7d50\u7684DNA\u5e8f\u5217\u5f62\u6210X\u578b\u69cb\u9020\uff08\u5716\u4e00\uff09\uff0c\u63a5\u8457\u7528\u63a5\u5408\u9176 (ligase) \u5c07X\u578bDNA\u5206\u5b50\u7684\u5169\u7aef\u9032\u884c\u5206\u5b50\u5167\u63a5\u5408 (intra-molecular ligation)\uff0c\u4ee5\u7522\u751f8\u5b57\u578b\u6216\u7d72\u5e36\u72c0DNA\u69cb\u9020\u3002\u518d\u4ee565\u2103\u5de6\u53f3\u9ad8\u6eab\u9032\u884c\u53cd\u9375\u7d50 (reverse cross-linking)\uff0c\u5c07\u7b2c\u4e00\u6b65\u7522\u751f\u7684\u76f8\u9130DNA\u5206\u5b50\u9593\u9375\u7d50\u6253\u958b\uff0c\u4f7f\u63a5\u5408\u7684\u5206\u5b50\u6062\u5fa9\u6210\u7dda\u72c0\u6216\u74b0\u72c0\u3002\u6700\u5f8c\uff0c\u4ee5\u5b9a\u91cf\u805a\u5408\u9176\u9023\u9396\u53cd\u61c9 (quantitative PCR, qPCR) \u653e\u5927\u7522\u7269\u53ca\u5f8c\u7e8c\u5b9a\u5e8f\u3002<\/p>\n

\u7531\u65bc\u76f8\u9130DNA\u5e8f\u5217\u6709\u8f03\u9ad8\u7684\u6a5f\u7387\u65bc\u5be6\u9a57\u7684\u7b2c\u4e00\u6b65\u4e2d\u7522\u751f\u9375\u7d50\uff0c\u4f7f\u5f97\u5be6\u9a57\u6700\u5f8c\u5b9a\u91cf\u805a\u5408\u9176\u9023\u9396\u53cd\u61c9\u4e2d\uff0c\u76f8\u9130\u5e8f\u5217\u6709\u8f03\u591a\u7684\u53cd\u61c9\u7522\u7269\u3002\u63a5\u8457\u4ee5\u5b9a\u5e8f\u7d50\u679c\u53cd\u63a8\u5e8f\u5217\u65bc\u57fa\u56e0\u9ad4\u4e0a\u7684\u4f4d\u7f6e (mapping)\uff0c\u5982\u6b64\u4fbf\u80fd\u63a8\u6e2c\u5f15\u5b50\u7684\u76ee\u6a19\u5e8f\u5217\u8207\u57fa\u56e0\u9ad4\u5167\u7684\u5176\u4ed6\u7279\u5b9a\u5e8f\u5217\uff0c\u5728\u7a7a\u9593\u4e0a\u5177\u6709\u4f55\u7a2e\u7a0b\u5ea6\u7684\u4ea4\u4e92\u4f5c\u7528\uff0c\u4e5f\u5c31\u80fd\u4f9d\u6b64\u5efa\u69cb\u4e00\u6bb5\u7279\u5b9aDNA\u5e8f\u5217\u7684\u67d3\u8272\u9ad4\u5728\u7d30\u80de\u6838\u5167\u76843D\u7d50\u69cb\u3002<\/p>\n

\u4f7f\u75283C\u6280\u8853\u6240\u5f97\u5230\u7684DNA\u7d50\u69cb\u5716\u8b5c (structure topology)\uff0c\u53ef\u7528\u4f86\u89e3\u91cbDNA\u7d50\u69cb\u4e0a\u7684\u6539\u8b8a\uff0c\u5305\u62ec\u76f4\u93c8\u5f62\u6210\u74b0\u5f62 (looping) DNA\uff0c\u5982\u4f55\u8abf\u63a7\u7279\u5b9a\u57fa\u56e0\u7684\u8868\u73fe\u3002\u9084\u6709\uff0c\u7531\u65bcDNA\u7247\u6bb5\u5728\u7a7a\u9593\u4e0a\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u6703\u9020\u6210\u67d3\u8272\u9ad4\u69cb\u578b\u4e0a\u7684\u6539\u8b8a\uff0c\u9032\u800c\u5f71\u97ff\u76f8\u95dc\u57fa\u56e0\u7684\u8abf\u63a7\uff0c\u56e0\u6b64\u53ef\u7814\u7a76\u5f37\u5316\u5b50\u548c\u555f\u52d5\u5b50\u5982\u4f55\u5f71\u97ff\u76ee\u6a19\u57fa\u56e0\u7684RNA\u8f49\u9304\u3002<\/p>\n

\"32102\"<\/a>

\u5716\u4e8c \u6a21\u64ec3C\u6280\u8853\u6240\u5f97\u4e4b\u5e8f\u5217\u4f4d\u7f6e\u5c0d\u7167\u805a\u5408\u9176\u53cd\u61c9\u7522\u7269\u5716\u8207DNA\u69cb\u578b\u5716\u8b5c\u3002\u5de6\u5716\u6a21\u64ec\u57fa\u56e0A\u7d93\u904e3C\u6280\u8853\u6240\u5f97\u4e4b\u4e0a\u4e0b\u6e38\u5e8f\u5217\u7247\u6bb5(1\u52307)\u805a\u5408\u9176\u9023\u9396\u53cd\u61c9\u7522\u91cf\u3002\u7531\u65bc\u805a\u5408\u9176\u53cd\u61c9\u7522\u7269\u91cf\u8207\u76f8\u9130DNA\u5e8f\u5217\u5728\u5be6\u9a57\u904e\u7a0b\u4e2d\u5f62\u6210\u7684\u9375\u7d50\u7387\u6210\u6b63\u76f8\u95dc\uff0c\u56e0\u6b64\u53ef\u4ee5\u7531\u7e31\u8ef8\u7684\u6578\u503c\u53cd\u61c9\u51fa\u7247\u6bb5\u4e4b\u9593\u5728\u7a7a\u9593\u4e0a\u7684\u9060\u8fd1\uff0c\u9032\u800c\u63a8\u6e2c\u51fa\u9577\u93c8DNA\u5728\u7a7a\u9593\u4e0a\u7684\u76f8\u4e92\u4f5c\u7528\u95dc\u4fc2\u5716\u8b5c\u3002\u5e8f\u5217\u7247\u6bb51\u52307\u4e2d\uff0c\u53ef\u80fd\u90e8\u5206\u70ba\u5df2\u77e5\u7684\u5f37\u5316\u5b50\uff0c\u53e6\u5916\u529f\u80fd\u5f9e\u672a\u88ab\u63cf\u8ff0\u4f46\u8207\u57fa\u56e0A\u6709\u76f8\u4e92\u4f5c\u7528\u7684\u5176\u4ed6\u7247\u6bb5\uff0c\u5247\u53ef\u80fd\u662f\u5177\u6709\u529f\u80fd\u7684\u5f37\u5316\u5b50\u3002\u56e0\u6b64\u53ef\u4ee5\u85c9\u75313C\u6280\u8853\u5f97\u5230\u65b0\u7684\u57fa\u56e0\u8abf\u63a7\u7247\u6bb5\u8207\u6a5f\u5236\u3002\uff08\u672c\u6587\u4f5c\u8005\u9673\u653f\u5100\u7e6a\uff09<\/p><\/div>\n

\u53e6\u5916\uff0c\u4ee5\u5f80\u529f\u80fd\u5f9e\u672a\u88ab\u63cf\u8ff0\u7684DNA\u5e8f\u5217\uff0c\u4e5f\u53ef\u56e0\u70ba3C\u6280\u8853\u7684\u61c9\u7528\uff0c\u5f97\u4ee5\u8b93\u7814\u7a76\u4eba\u54e1\u5f9e\u5e8f\u5217\u8207\u57fa\u56e0\u7247\u6bb5\u7684\u4ea4\u4e92\u4f5c\u7528\u4e2d\uff0c\u9810\u6e2c\u51fa\u65b0\u7684\u57fa\u56e0\u8868\u73fe\u8abf\u63a7\u6a5f\u5236\uff08\u5716\u4e8c\uff0cJin et al., 2013\uff09\u3002\u56e0\u6b64\uff0c3C\u6280\u8853\u7684\u767c\u5c55\u70ba\u57fa\u56e0\u8868\u73fe\u7684\u7814\u7a76\u5e36\u4f86\u4e86\u76f8\u7576\u5927\u7684\u7a81\u7834\u3002<\/p>\n

\u7136\u800c3C\u6280\u8853\u4e5f\u4e0d\u662f\u5168\u7136\u6c92\u6709\u9650\u5236\uff0c\u7531\u65bc\u5927\u90e8\u5206\u96d9\u500d\u9ad4\u751f\u7269\u7684\u57fa\u56e0\u53ea\u6709\u4e00\u5c0d\u5e8f\u5217\uff0c\u91dd\u5c0d\u57fa\u56e0\u9ad4\u4e2d\u6578\u767e\u842c\u9e7c\u57fa\u5c0d\u9032\u884c\u653e\u5927\u6642\uff0c\u7a00\u5c11\u7247\u6bb5\u6240\u5f97\u5230\u7684\u8a0a\u865f\u5f80\u5f80\u5bb9\u6613\u88ab\u975e\u5c08\u4e00\u6027\u9375\u7d50\u7684\u96dc\u8a0a\u7d66\u8986\u84cb\u3002\u56e0\u6b64\u5c0d\u7167\u7d44\u6311\u9078\u3001\u8b39\u614e\u7684\u5be6\u9a57\u8a2d\u8a08\u3001\u5be6\u9a57\u6578\u64da\u7684\u6b63\u78ba\u89e3\u8b80\uff08\u6700\u5e38\u767c\u751f\u7684\u662f\u7b2c\u4e00\u578b\u932f\u8aa4\uff1a\u5c07\u5be6\u969b\u4e0a\u4e0d\u5b58\u5728\u7684\u5e8f\u5217\u4ea4\u4e92\u4f5c\u7528\u5224\u65b7\u70ba\u5b58\u5728\uff09\uff0c\u6709\u53ef\u80fd\u6703\u9020\u62103C\u5be6\u9a57\u7d50\u679c\u5224\u5b9a\u4e0a\u7684\u56f0\u96e3\u3002\u53e6\u5916\uff0c\u7531\u65bc3C\u6280\u8853\u91dd\u5c0d\u76ee\u6a19\u5e8f\u5217\u4ee5\u805a\u5408\u9176\u9023\u9396\u53cd\u61c9\u9032\u884c\u653e\u5927\uff0c\u5728\u4e00\u6b21\u5be6\u9a57\u8a2d\u8a08\u4e2d\u8981\u63a2\u8a0e\u6574\u500b\u57fa\u56e0\u9ad4\u5e8f\u5217\u7684\u4ea4\u4e92\u4f5c\u7528\u5fc5\u9808\u6e96\u5099\u76f8\u7576\u591a\u7684\u5f15\u5b50\u5c0d\uff0c\u4ecd\u7136\u9650\u5236\u5168\u57fa\u56e0\u9ad43D\u7d50\u69cb\u7684\u5206\u6790 (de Wit & de Laat, 2012)\u3002<\/p>\n

\u96a8\u8457\u751f\u7269\u6676\u7247 (microarray) \u4ee5\u53ca\u66f4\u4fbf\u5b9c\u4e14\u9ad8\u901a\u91cf (high-throughput) \u7684\u6b21\u4e16\u4ee3\u5b9a\u5e8f (next generation sequencing\uff0cNGS) \u9678\u7e8c\u767c\u5c55\uff0c\u4ee53C\u70ba\u57fa\u790e\u76844C (chromosome conformation capture-on-chip\uff0c\u6676\u7247\u67d3\u8272\u9ad4\u7d50\u69cb\u6355\u6349\uff0c\u6216circular chromosome conformation capture\uff0c\u74b0\u72c0\u67d3\u8272\u9ad4\u7d50\u69cb\u6355\u6349)\u30015C (chromosome conformation capture carbon copy\uff0c\u901a\u7528\u5f15\u5b50\u67d3\u8272\u9ad4\u7d50\u69cb\u6355\u6349) \u6216 HiC \u7b49\u6280\u8853\uff08\u5716\u4e00\uff09\uff0c\u88ab\u8a2d\u8a08\u4e26\u61c9\u7528\u4ee5\u89e3\u69cb\u4e00\u689d\u5e36\u6709\u6578\u5104\u9e7c\u57fa\u5c0d\u67d3\u8272\u9ad4\u7684\u69cb\u578b (Lieberman-Aiden et al., 2009)\uff0c\u6216\u63d0\u5347\u5230\u6578\u5343\u500b\u9e7c\u57fa\u5c0d\u4ee5\u4e0b\u7684\u89e3\u6790\u5ea6\uff08\u4e00\u822c\u771f\u6838\u751f\u7269\u57fa\u56e0\u7684\u5916\u986f\u5b50 (exon) \u5927\u7d04\u5e36\u6709\u4e00\u81f3\u5169\u5343\u500b\u9e7c\u57fa\u5c0d\uff09\uff0c\u4f7f\u79d1\u5b78\u5bb6\u80fd\u5920\u66f4\u7cbe\u78ba\u5730\u9810\u6e2c\u53ef\u80fd\u7684\u57fa\u56e0\u8abf\u63a7\u5e8f\u5217\u53ca\u67d3\u8272\u9ad4\u7d50\u69cb\u3002<\/p>\n

\n

\u53c3\u8003\u6587\u737b<\/b><\/strong><\/p>\n

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