Segueni Julie, Noordermeer Daan
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Comput Struct Biotechnol J. 2022 May 27;20:2685-2698. doi: 10.1016/j.csbj.2022.05.044. eCollection 2022.
The emergence and progression of cancers is accompanied by a dysregulation of transcriptional programs. The three-dimensional (3D) organization of the human genome has emerged as an important multi-level mediator of gene transcription and regulation. In cancer cells, this organization can be restructured, providing a framework for the deregulation of gene activity. The CTCF protein, initially identified as the product from a tumor suppressor gene, is a jack-of-all-trades for the formation of 3D genome organization in normal cells. Here, we summarize how CTCF is involved in the multi-level organization of the human genome and we discuss emerging insights into how perturbed CTCF function and DNA binding causes the activation of oncogenes in cancer cells, mostly through a process of enhancer hijacking. Moreover, we highlight non-canonical functions of CTCF that can be relevant for the emergence of cancers as well. Finally, we provide guidelines for the computational identification of perturbed CTCF binding and reorganized 3D genome structure in cancer cells.
癌症的发生和发展伴随着转录程序的失调。人类基因组的三维（3D）组织已成为基因转录和调控的重要多层次调节因子。在癌细胞中，这种组织可以被重新构建，为基因活性的失调提供了一个框架。CTCF蛋白最初被鉴定为一种肿瘤抑制基因的产物，是正常细胞中3D基因组组织形成的多面手。在这里，我们总结了CTCF如何参与人类基因组的多层次组织，并讨论了关于CTCF功能和DNA结合受到干扰如何导致癌细胞中癌基因激活的新见解，这主要是通过增强子劫持过程实现的。此外，我们还强调了CTCF的非规范功能，这些功能也可能与癌症的发生有关。最后，我们提供了在癌细胞中通过计算识别CTCF结合受干扰和3D基因组结构重组的指导方针。
