Enhancer Features that Drive Formation of Transcriptional Condensates
Enhancer Features that Drive Formation of Transcriptional Condensates
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DOI：
10.1016/j.molcel.2019.07.009
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发表时间：
2019-08-08
期刊：
影响因子：
16
通讯作者：
Chakraborty, Arup K.
中科院分区：
文献类型：
--
作者：
Shrinivas, Krishna;Sabari, Benjamin R.;Chakraborty, Arup K.
增强子是由转录因子（TF）结合的DNA元件，其将共激活因子和转录机器募集到基因。相分离的TF和共激活剂的缩合物已经被牵连在组装转录机器在特定的增强子，但在这个过程中的DNA序列的作用还没有被探索。我们发现，DNA序列编码TF结合位点的数量，密度和亲和力高于明确定义的阈值驱动TF和辅激活剂的冷凝。特异性结构化（TF-DNA）和弱多价（TF-共激活因子）相互作用的组合允许在由DNA序列和表达的TF的互补物确定的特定基因组基因座处形成缩合物。发现驱动缩合的DNA特征促进细胞中的增强子活性和转录。我们的研究提供了一个框架，以了解基因组如何可以支架转录缩合物在特定的位点，以及如何相分离的普遍现象可能会调节这一过程。
Enhancers are DNA elements that are bound by transcription factors (TFs), which recruit coactivators and the transcriptional machinery to genes. Phase-separated condensates of TFs and coactivators have been implicated in assembling the transcription machinery at particular enhancers, yet the role of DNA sequence in this process has not been explored. We show that DNA sequences encoding TF binding site number, density, and affinity above sharply defined thresholds drive condensation of TFs and coactivators. A combination of specific structured (TF-DNA) and weak multivalent (TF-coactivator) interactions allows for condensates to form at particular genomic loci determined by the DNA sequence and the complement of expressed TFs. DNA features found to drive condensation promote enhancer activity and transcription in cells. Our study provides a framework to understand how the genome can scaffold transcriptional condensates at specific loci and how the universal phenomenon of phase separation might regulate this process.