Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Genetics. 2022 Sep 30;222(2). doi: 10.1093/genetics/iyac111.
Transcription factors regulate gene expression by binding to regulatory DNA and recruiting regulatory protein complexes. The DNA-binding and protein-binding functions of transcription factors are traditionally described as independent functions performed by modular protein domains. Here, I argue that genome binding can be a 2-part process with both DNA-binding and protein-binding steps, enabling transcription factors to perform a 2-step search of the nucleus to find their appropriate binding sites in a eukaryotic genome. I support this hypothesis with new and old results in the literature, discuss how this hypothesis parsimoniously resolves outstanding problems, and present testable predictions.
转录因子通过与调控 DNA 结合并募集调控蛋白复合物来调节基因表达。转录因子的 DNA 结合和蛋白结合功能传统上被描述为模块化蛋白结构域执行的独立功能。在这里，我认为基因组结合可以是一个具有 DNA 结合和蛋白结合步骤的两步过程，使转录因子能够在真核基因组中进行核内两步搜索，以找到其适当的结合位点。我用文献中的新结果和旧结果支持这个假说，讨论这个假说如何简洁地解决了悬而未决的问题，并提出了可测试的预测。
