Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Cell. 2018 Feb 8;172(4):650-665. doi: 10.1016/j.cell.2018.01.029.
Transcription factors (TFs) recognize specific DNA sequences to control chromatin and transcription, forming a complex system that guides expression of the genome. Despite keen interest in understanding how TFs control gene expression, it remains challenging to determine how the precise genomic binding sites of TFs are specified and how TF binding ultimately relates to regulation of transcription. This review considers how TFs are identified and functionally characterized, principally through the lens of a catalog of over 1,600 likely human TFs and binding motifs for two-thirds of them. Major classes of human TFs differ markedly in their evolutionary trajectories and expression patterns, underscoring distinct functions. TFs likewise underlie many different aspects of human physiology, disease, and variation, highlighting the importance of continued effort to understand TF-mediated gene regulation.
转录因子（TFs）识别特定的 DNA 序列以控制染色质和转录，形成一个复杂的系统，指导基因组的表达。尽管人们对理解 TFs 如何控制基因表达非常感兴趣，但确定 TFs 的精确基因组结合位点是如何指定的以及 TF 结合如何最终与转录调控相关仍然具有挑战性。本综述考虑了如何通过超过 1600 种可能的人类 TFs 的目录以及其中三分之二的结合基序的视角来鉴定和功能表征 TFs。人类 TFs 的主要类别在进化轨迹和表达模式上有明显差异，突出了其不同的功能。TFs 同样也是人类生理学、疾病和变异的许多不同方面的基础，突出了继续努力理解 TF 介导的基因调控的重要性。
