Oncode Institute and Division of Gene Regulation, the Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, the Netherlands.
Oncode Institute and Division of Gene Regulation, the Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, the Netherlands
Essays Biochem. 2019 Apr 23;63(1):157-165. doi: 10.1042/EBC20180069.
Orchestrating vertebrate genomes require a complex interplay between the linear composition of the genome and its 3D organization inside the nucleus. This requires the function of specialized proteins, able to tune various aspects of genome organization and gene regulation. The CCCTC-binding factor (CTCF) is a DNA binding factor capable of regulating not only the 3D genome organization, but also key aspects of gene expression, including transcription activation and repression, RNA splicing, and enhancer/promoter insulation. A growing body of evidence proposes that CTCF, together with cohesin contributes to DNA loop formation and 3D genome organization. CTCF binding sites are mutation hotspots in cancer, while mutations in CTCF itself lead to intellectual disabilities, emphasizing its importance in disease etiology. In this review we cover various aspects of CTCF function, revealing the polyvalence of this factor as a highly diversified tool for vertebrate genome organization and transcription regulation.
脊椎动物基因组的调控需要线性基因组组成与其在核内的 3D 组织之间的复杂相互作用。这需要专门蛋白质的功能，这些蛋白质能够调整基因组组织和基因调控的各个方面。CCCTC 结合因子（CTCF）是一种 DNA 结合因子，能够调节不仅 3D 基因组组织，而且还包括基因表达的关键方面，包括转录激活和抑制、RNA 剪接以及增强子/启动子隔离。越来越多的证据表明，CTCF 与黏合蛋白一起有助于 DNA 环形成和 3D 基因组组织。CTCF 结合位点是癌症中的突变热点，而 CTCF 自身的突变会导致智力障碍，强调了其在疾病发病机制中的重要性。在这篇综述中，我们涵盖了 CTCF 功能的各个方面，揭示了该因子作为脊椎动物基因组组织和转录调控的高度多样化工具的多功能性。
