Zhongshan Hospital Institute of Clinical Science, Fudan University Medical School, Shanghai Institute of Clinical Bioinformatics Shanghai, China.
Zhongshan Hospital Institute of Clinical Science, Fudan University Medical School, Shanghai Institute of Clinical Bioinformatics Shanghai, China.
Semin Cell Dev Biol. 2019 Jun;90:138-143. doi: 10.1016/j.semcdb.2018.07.010. Epub 2018 Jul 21.
Polycomb group proteins (PcG) play important roles in the maintenance of DNA sequencing and multi-dimensional organization of genome. The main PcG complexes are consisted of Polycomb repressive complex 1 and 2, of which the diversity is dependent upon target gene sequences and functions. The present review initially explores the mechanism-based relationship and functional roles of PcG proteins in the interplay between epithelial mesenchymal transition (EMT) and chromatin dynamics in lung cancer. PcG proteins regulate the target genes by modifying histone and chromosome conformation and influencing chromatin looping and long-range interactions between topologically associating domains (TADs). PcG proteins regulate target genes expression and long-distance interactions between TADs in nucleus in the development of EMT and lung cancer. PcG plays decisive regulatory roles in epithelial differentiation and transition or signaling and activation of oncogenes, by promoting the isoforms at the transcriptional levels, to drive EMT to greater invasive ability and carcinogenesis. With the development of single cell systems biology and gene editing, PcG roles in 3D genome organization, heterogeneity, and EMT will be furthermore understood at single cell levels.
多梳蛋白家族(PcG)在维持 DNA 测序和基因组的多维组织中发挥重要作用。主要的 PcG 复合物由多梳抑制复合物 1 和 2 组成,其多样性取决于靶基因序列和功能。本综述最初探讨了 PcG 蛋白在肺癌中上皮间质转化(EMT)和染色质动力学相互作用中的基于机制的关系和功能作用。PcG 蛋白通过修饰组蛋白和染色体构象以及影响染色质环化和拓扑关联域(TAD)之间的长程相互作用来调节靶基因。PcG 蛋白在 EMT 和肺癌的发展过程中,通过促进转录水平的异构体,调节核内靶基因的表达和 TAD 之间的长距离相互作用。PcG 通过促进转录水平的异构体,在促进上皮分化和过渡或信号转导和癌基因激活方面发挥决定性的调控作用,从而推动 EMT 向更大的侵袭能力和癌变发展。随着单细胞系统生物学和基因编辑的发展,PcG 在 3D 基因组组织、异质性和 EMT 中的作用将在单细胞水平上得到进一步理解。