Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA
Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, California Institute for Regenerative Medicine Center of Excellence, University of California, Berkeley, Berkeley, CA
J Cell Biol. 2018 Apr 2;217(4):1181-1191. doi: 10.1083/jcb.201710038. Epub 2018 Jan 29.
The assembly of sequence-specific enhancer-binding transcription factors (TFs) at cis-regulatory elements in the genome has long been regarded as the fundamental mechanism driving cell type-specific gene expression. However, despite extensive biochemical, genetic, and genomic studies in the past three decades, our understanding of molecular mechanisms underlying enhancer-mediated gene regulation remains incomplete. Recent advances in imaging technologies now enable direct visualization of TF-driven regulatory events and transcriptional activities at the single-cell, single-molecule level. The ability to observe the remarkably dynamic behavior of individual TFs in live cells at high spatiotemporal resolution has begun to provide novel mechanistic insights and promises new advances in deciphering causal-functional relationships of TF targeting, genome organization, and gene activation. In this review, we review current transcription imaging techniques and summarize converging results from various lines of research that may instigate a revision of models to describe key features of eukaryotic gene regulation.
序列特异性增强子结合转录因子（TFs）在基因组顺式调控元件上的组装，长期以来一直被认为是驱动细胞类型特异性基因表达的基本机制。然而，尽管在过去的三十年中进行了广泛的生化、遗传和基因组研究，我们对增强子介导的基因调控的分子机制的理解仍然不完整。最近成像技术的进步现在能够在单细胞、单分子水平上直接可视化 TF 驱动的调控事件和转录活性。以高时空分辨率观察活细胞中单个 TF 的显著动态行为的能力，开始提供新的机制见解，并有望在破译 TF 靶向、基因组组织和基因激活的因果功能关系方面取得新的进展。在这篇综述中，我们回顾了当前的转录成像技术，并总结了来自不同研究领域的汇聚结果，这些结果可能会促使对模型进行修订，以描述真核基因调控的关键特征。
