Muñoz Victor, Goluguri Rama Reddy, Ghosh Catherine, Tanielian Benjamin, Sadqi Mourad
CREST Center for Cellular and Biomolecular Machines, University of California, Merced, California, USA; email:
Department of Bioengineering, University of California, Merced, California, USA.
Annu Rev Biophys. 2025 May;54(1):121-139. doi: 10.1146/annurev-biophys-071524-111008. Epub 2025 Jan 29.
Like their prokaryotic counterparts, eukaryotic transcription factors must recognize specific DNA sites, search for them efficiently, and bind to them to help recruit or block the transcription machinery. For eukaryotic factors, however, the genetic signals are extremely complex and scattered over vast, multichromosome genomes, while the DNA interplay occurs in a varying landscape defined by chromatin remodeling events and epigenetic modifications. Eukaryotic factors are rich in intrinsically disordered regions and are also distinct in their recognition of short DNA motifs and utilization of open DNA interaction interfaces as ways to gain access to DNA on nucleosomes. Recent findings are revealing the profound, unforeseen implications of such characteristics for the mechanisms of DNA interplay. In this review we discuss these implications and how they are shaping the eukaryotic transcription control paradigm into one of promiscuous signal recognition, highly dynamic interactions, heterogeneous DNA scanning, and multiprong conformational control.
与原核生物中的对应物一样,真核生物转录因子必须识别特定的DNA位点,高效地寻找它们,并与之结合,以帮助招募或阻断转录机制。然而,对于真核生物因子而言,遗传信号极其复杂,分散在庞大的多染色体基因组中,而DNA相互作用发生在由染色质重塑事件和表观遗传修饰所定义的不断变化的环境中。真核生物因子富含内在无序区域,在识别短DNA基序以及利用开放DNA相互作用界面以接触核小体上的DNA方面也有所不同。最近的研究结果揭示了这些特征对DNA相互作用机制产生的深刻、意想不到的影响。在这篇综述中,我们讨论了这些影响,以及它们如何将真核生物转录控制范式塑造成一种混杂信号识别、高度动态相互作用、异质DNA扫描和多管构象控制的范式。