Segal Eran, Widom Jonathan
Department of Computer Science and Applied Mathematics and Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Nat Rev Genet. 2009 Jul;10(7):443-56. doi: 10.1038/nrg2591.
Complex transcriptional behaviours are encoded in the DNA sequences of gene regulatory regions. Advances in our understanding of these behaviours have been recently gained through quantitative models that describe how molecules such as transcription factors and nucleosomes interact with genomic sequences. An emerging view is that every regulatory sequence is associated with a unique binding affinity landscape for each molecule and, consequently, with a unique set of molecule-binding configurations and transcriptional outputs. We present a quantitative framework based on existing methods that unifies these ideas. This framework explains many experimental observations regarding the binding patterns of factors and nucleosomes and the dynamics of transcriptional activation. It can also be used to model more complex phenomena such as transcriptional noise and the evolution of transcriptional regulation.
复杂的转录行为编码在基因调控区域的DNA序列中。最近，通过定量模型增进了我们对这些行为的理解，这些模型描述了转录因子和核小体等分子如何与基因组序列相互作用。一种新出现的观点认为，每个调控序列对于每个分子都有独特的结合亲和力图谱，因此，具有独特的一组分子结合构型和转录输出。我们基于现有方法提出了一个定量框架，该框架统一了这些观点。这个框架解释了许多关于因子和核小体结合模式以及转录激活动态的实验观察结果。它还可用于对转录噪声和转录调控进化等更复杂的现象进行建模。
