eRNA co-expression network uncovers TF dependency and convergent cooperativity.
eRNA co-expression network uncovers TF dependency and convergent cooperativity.
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DOI：
10.1038/s41598-023-46415-2
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发表时间：
2023-11-04
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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增强子RNA（eRNA）是由转录增强子产生的与其活性高度相关的非编码RNA。在67个个体的人类淋巴母细胞系中使用加帽新生RNA测序（PRO-cap）数据集，我们在增强子和启动子中鉴定了超过8万个转录转录调控元件（tTREs）表达的个体间变异。跨个体tTRE的eRNA共表达分析揭示了增强子如何相互关联以及与启动子的关联。中远程共表达表现出距离依赖性衰减，TF占用修改。特别地，我们发现了一类“二价”TF，包括粘附素，其根据其拓扑结构促进和隔离增强子和/或启动子之间的相互作用。在短距离，我们观察到附近的eRNA在收敛和发散方向之间的链特异性相关性。我们的研究结果支持了会聚eRNA的合作模型，与eRNA促进相邻增强子而不是相互干扰一致。因此，我们的方法来推断功能的相互作用，从共表达分析增强子相互作用的距离，方向和结合的TF景观的函数的原则提供了新的见解。
Enhancer RNAs (eRNAs) are non-coding RNAs produced by transcriptional enhancers that are highly correlated with their activity. Using a capped nascent RNA sequencing (PRO-cap) dataset in human lymphoblastoid cell lines across 67 individuals, we identified inter-individual variation in the expression of over 80 thousand transcribed transcriptional regulatory elements (tTREs), in both enhancers and promoters. Co-expression analysis of eRNAs from tTREs across individuals revealed how enhancers are associated with each other and with promoters. Mid- to long-range co-expression showed a distance-dependent decay that was modified by TF occupancy. In particular, we found a class of “bivalent” TFs, including Cohesin, that both facilitate and isolate the interaction between enhancers and/or promoters, depending on their topology. At short distances, we observed strand-specific correlations between nearby eRNAs in both convergent and divergent orientations. Our results support a cooperative model of convergent eRNAs, consistent with eRNAs facilitating adjacent enhancers rather than interfering with each other. Therefore, our approach to infer functional interactions from co-expression analyses provided novel insights into the principles of enhancer interactions as a function of distance, orientation, and binding landscapes of TFs.
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影响因子：
12.3
作者：
Melgar MF;Collins FS;Sethupathy P
通讯作者：
Sethupathy P
影响因子：
9.8
作者：
Gusev, Alexander;Lee, S. Hong;Price, Alkes L.
通讯作者：
Price, Alkes L.
影响因子：
5.6
作者：
Barutcu AR;Fritz AJ;Zaidi SK;van Wijnen AJ;Lian JB;Stein JL;Nickerson JA;Imbalzano AN;Stein GS
通讯作者：
Stein GS
影响因子：
9.9
作者：
Lefebvre, Celine;Rajbhandari, Presha;Alvarez, Mariano J.;Bandaru, Pradeep;Lim, Wei Keat;Sato, Mai;Wang, Kai;Sumazin, Pavel;Kustagi, Manjunath;Bisikirska, Brygida C.;Basso, Katia;Beltrao, Pedro;Krogan, Nevan;Gautier, Jean;Dalla-Favera, Riccardo;Califano, Andrea
通讯作者：
Califano, Andrea
DOI：
10.1126/science.1222794
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maurano MT;Humbert R;Rynes E;Thurman RE;Haugen E;Wang H;Reynolds AP;Sandstrom R;Qu H;Brody J;Shafer A;Neri F;Lee K;Kutyavin T;Stehling-Sun S;Johnson AK;Canfield TK;Giste E;Diegel M;Bates D;Hansen RS;Neph S;Sabo PJ;Heimfeld S;Raubitschek A;Ziegler S;Cotsapas C;Sotoodehnia N;Glass I;Sunyaev SR;Kaul R;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA