Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada and Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
Nucleic Acids Res. 2013 Oct;41(19):8822-41. doi: 10.1093/nar/gkt578. Epub 2013 Aug 2.
In higher organisms, gene regulation is controlled by the interplay of non-random combinations of multiple transcription factors (TFs). Although numerous attempts have been made to identify these combinations, important details, such as mutual positioning of the factors that have an important role in the TF interplay, are still missing. The goal of the present work is in silico mapping of some of such associating factors based on their mutual positioning, using computational screening. We have selected the process of myogenesis as a study case, and we focused on TF combinations involving master myogenic TF Myogenic differentiation (MyoD) with other factors situated at specific distances from it. The results of our work show that some muscle-specific factors occur together with MyoD within the range of ±100 bp in a large number of promoters. We confirm co-occurrence of the MyoD with muscle-specific factors as described in earlier studies. However, we have also found novel relationships of MyoD with other factors not specific for muscle. Additionally, we have observed that MyoD tends to associate with different factors in proximal and distal promoter areas. The major outcome of our study is establishing the genome-wide connection between biological interactions of TFs and close co-occurrence of their binding sites.
在高等生物中，基因调控是由多个转录因子（TFs）的非随机组合相互作用控制的。尽管已经有许多尝试来识别这些组合，但重要的细节，如在 TF 相互作用中起重要作用的因素的相互定位，仍然缺失。本工作的目的是基于其相互定位，通过计算筛选来对一些关联因子进行计算机绘图。我们选择肌发生过程作为研究案例，并且集中研究涉及主肌生成 TF 肌生成分化（MyoD）与位于其特定距离处的其他因子的 TF 组合。我们工作的结果表明，在许多启动子中，一些肌肉特异性因子与 MyoD 一起出现在±100bp 的范围内。我们证实了 MyoD 与肌肉特异性因子的共同出现，如早期研究所述。然而，我们也发现了 MyoD 与非肌肉特异性的其他因子之间的新关系。此外，我们还观察到 MyoD 倾向于在近端和远端启动子区域与不同的因子结合。我们研究的主要结果是建立了 TF 生物相互作用与它们的结合位点紧密共现之间的全基因组联系。
