超级增强子的转录相分离模型与肿瘤研究进展

Transcriptional Phase Separation Model of Super-Enhancers and Advances in Cancer Research

超级增强子(super-enhancers,SEs)是驱动高转录水平的增强子簇。SEs驱动的基因网络在决定细胞身份方面发挥着重要作用。最近,在SEs驱动的关键癌基因转录模型中引入了相分离(phase separation,PS)的概念。该文系统地讨论了转录PS模型里的主要元素,通过分子间的作用力总结归纳了元素之间的关系,并讲述了从SEs形成到转录激活延伸的事件。在表观遗传/基因改变下,SEs驱动的癌基因促进肿瘤的发生、进展、转移和耐药。生物物理学学科重新激发了科学家对肿瘤转录调控的思考。

SEs(super-enhancers)are clusters of enhancers that drive a high transcription level.SEs driven genes network play prominent roles in the decision of cell identity.Recently,PS(phase separation)of transcriptional machinery was reported as a model to explain high expression in proximal SEs.This review systematically discusses the principal factors in PS of transcriptional machinery.The relationship amongst factors by intermolecular force tells a story from SEs forming to transcriptional activation.Under epigenetic/genetic alterations,SEs driven oncogenes promote tumorigenesis,progression,metastasis,and drug resistance in cancer.Physical biology has renewed scientists’thinking on the regulation of cancer cells transcription.