Interactions between pluripotency factors specify cis-regulation in embryonic stem cells.
Interactions between pluripotency factors specify cis-regulation in embryonic stem cells.
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DOI：
10.1101/gr.200733.115
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发表时间：
2016-06
期刊：
影响因子：
7
通讯作者：
Cohen BA
中科院分区：
文献类型：
--
作者：
Fiore C;Cohen BA
我们研究了多能性转录因子（TF）之间的相互作用如何影响顺式调节。我们创建了数百个合成的顺式调节元件（克雷斯），由多能性TF的结合位点组合组成，并测量了它们在小鼠胚胎干细胞（ES）中的表达。结合TF之间的相互作用的热力学模型解释了这些克雷斯表达的大部分（72%）的方差。这些相互作用包括TF之间的三种有利的异型相互作用。该模型还预测了一个不利的同型之间的相互作用的TF，有助于解释的观察，同型链的结合位点表达在低水平。我们进一步研究了由KLF4结合位点的同型链组成的克雷斯驱动的表达。我们的研究结果表明，KLF同系物作出独特的贡献，这些克雷斯的监管。我们得出结论，多能性TF之间的一组特定的相互作用在设定ES细胞中克雷斯驱动的表达水平中起着重要作用。
We investigated how interactions between pluripotency transcription factors (TFs) affect cis-regulation. We created hundreds of synthetic cis-regulatory elements (CREs) comprised of combinations of binding sites for pluripotency TFs and measured their expression in mouse embryonic stem (ES) cells. A thermodynamic model that incorporates interactions between TFs explains a large portion (72%) of the variance in expression of these CREs. These interactions include three favorable heterotypic interactions between TFs. The model also predicts an unfavorable homotypic interaction between TFs, helping to explain the observation that homotypic chains of binding sites express at low levels. We further investigated the expression driven by CREs comprised of homotypic chains of KLF4 binding sites. Our results suggest that KLF homologs make unique contributions to regulation by these CREs. We conclude that a specific set of interactions between pluripotency TFs plays a large role in setting the levels of expression driven by CREs in ES cells.