Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers.
Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers.
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DOI：
10.1093/nar/gkt374
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发表时间：
2013-08
影响因子：
14.9
通讯作者：
Hannenhalli S
中科院分区：
文献类型：
--
作者：
Malin J;Aniba MR;Hannenhalli S
哺乳动物基因表达通常受远端增强子调控。然而，很少有人知道更高阶的功能组织的增强子。使用100 K P300结合区域作为候选增强子，我们基于DNA酶超敏性研究了它们在72种细胞类型中的相关活性。我们发现增强子之间的广泛相关活性，其随着增强子间基因组距离的增加而降低。我们发现，相关的增强子往往共享共同的转录因子（TF）结合基序，和几个染色质修饰酶优先与这些TF相互作用。增强子对中共享基序的存在可以以73%的准确度预测相关活性。此外，相关增强子附近的基因表现出相关的表达和共享共同的功能。相关的增强子往往在空间上接近。有趣的是，相对于强增强子，弱增强子倾向于与显著更大数量的其他增强子相关。此外，强/弱增强子分别优先与强/弱增强子相关。我们构建了增强子网络的基础上共享的基序和相关的活动，并显示出显着的功能富集在其推定的靶基因簇。总的来说，我们的分析显示增强子之间的广泛相关活性，并揭示了增强子的活性受多种潜在机制的协调调节，这些机制涉及共享TF结合，染色质修饰酶和3D染色质结构，最终共同调节功能相关的基因。
Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using ∼100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes.
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影响因子：
12.3
作者：
Berman BP;Pfeiffer BD;Laverty TR;Salzberg SL;Rubin GM;Eisen MB;Celniker SE
通讯作者：
Celniker SE
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.8
作者：
Sanyal, Amartya;Lajoie, Bryan R.;Jain, Gaurav;Dekker, Job
通讯作者：
Dekker, Job
影响因子：
12.3
作者：
Li XY;Thomas S;Sabo PJ;Eisen MB;Stamatoyannopoulos JA;Biggin MD
通讯作者：
Biggin MD
影响因子：
2.5
作者：
Levy, S;Hannenhalli, S
通讯作者：
Hannenhalli, S