Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.
Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells.
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DOI：
10.1126/science.1259418
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发表时间：
2015-02-27
期刊：
影响因子：
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通讯作者：
Hayashizaki Y
中科院分区：
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作者：
Arner E;Daub CO;Vitting-Seerup K;Andersson R;Lilje B;Drabløs F;Lennartsson A;Rönnerblad M;Hrydziuszko O;Vitezic M;Freeman TC;Alhendi AM;Arner P;Axton R;Baillie JK;Beckhouse A;Bodega B;Briggs J;Brombacher F;Davis M;Detmar M;Ehrlund A;Endoh M;Eslami A;Fagiolini M;Fairbairn L;Faulkner GJ;Ferrai C;Fisher ME;Forrester L;Goldowitz D;Guler R;Ha T;Hara M;Herlyn M;Ikawa T;Kai C;Kawamoto H;Khachigian LM;Klinken SP;Kojima S;Koseki H;Klein S;Mejhert N;Miyaguchi K;Mizuno Y;Morimoto M;Morris KJ;Mummery C;Nakachi Y;Ogishima S;Okada-Hatakeyama M;Okazaki Y;Orlando V;Ovchinnikov D;Passier R;Patrikakis M;Pombo A;Qin XY;Roy S;Sato H;Savvi S;Saxena A;Schwegmann A;Sugiyama D;Swoboda R;Tanaka H;Tomoiu A;Winteringham LN;Wolvetang E;Yanagi-Mizuochi C;Yoneda M;Zabierowski S;Zhang P;Abugessaisa I;Bertin N;Diehl AD;Fukuda S;Furuno M;Harshbarger J;Hasegawa A;Hori F;Ishikawa-Kato S;Ishizu Y;Itoh M;Kawashima T;Kojima M;Kondo N;Lizio M;Meehan TF;Mungall CJ;Murata M;Nishiyori-Sueki H;Sahin S;Nagao-Sato S;Severin J;de Hoon MJ;Kawai J;Kasukawa T;Lassmann T;Suzuki H;Kawaji H;Summers KM;Wells C;FANTOM Consortium;Hume DA;Forrest AR;Sandelin A;Carninci P;Hayashizaki Y
虽然人们普遍认为细胞分化需要改变转录网络，但以前还没有对特定基因集上的启动子和增强子的动态调节进行整体研究。利用活性启动子和增强子被转录的事实，我们同时测量了它们在19个人类和14个小鼠的时间过程中的活性，涵盖了广泛的细胞类型和生物刺激。增强子RNA，然后是编码转录因子的信使RNA，主导了最早的反应。关键谱系转录因子的结合位点同时在每个细胞系统中活跃的增强子和启动子中过度表达。我们的数据支持一个高度概括的模型，在该模型中，增强子转录是细胞分化或激活过程中连续转录变化波中最早的事件。
Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation.