1q42.3染色质区域一个前列腺癌特异性超级增强子样元件通过染色质相互作用促进细胞迁移

A Prostate Cancer Specific Super Enhancer in Risk Chr1q42.3 Locus Promotes Cell Migration Through Chromatin Interaction

前列腺癌在全球男性中发病率居于前列,遗传因素是影响前列腺癌发生发展的主要因素.研究报道1号染色体长臂42区3带至43区(1q42.3-43)存在一个潜在的前列腺癌易感染色体座位.但这个易感座位与肿瘤关联的分子机制迄今未得到确认.增强子是能够改变染色质活化状态的DNA序列,通过精准调控基因时空表达从而决定细胞身份命运.通过ChIP-seq发现1q42.3染色质区域存在一个前列腺癌特异性超级增强子样元件;利用CRISPR/Cas9系统敲除该区段后发现细胞迁移能力明显降低,并利用RNA-seq筛选出多个差异表达的基因;通过Hi-C鉴定出与该超级增强子样元件相互作用的染色质区段:最后将RNA-seq和Hi-C进行综合分析预测出该超级增强子样元件直接调控的基因.

Prostate cancer(PCa) is one of the most common health threats for men. Notably, genetic factors may contribute as much as 42% to the risk of prostate cancer,which is the highest among all cancer types. Super-enhancers(SEs) play an important role in regulating cell type specific gene expression,and genes expression profile can be affected by 3-D chromatin interactions. Previous studies by linkage analysis have proposed a predisposing locus for PCa on chromosome 1q42.2-43. Here, a PCa-specific super-enhancer-like element was identified in 1q42.3 locus through ChIP-seq analysis. Then, CRISPR/Cas9 mediated knock out experiment shows this region plays a key role in promoting cell migration. Integrative analysis of RNA-seq and Hi-C data suggests that the PCa specific SE-Like element in 1q42.3 can directly regulate cell migration related genes through long range chromatin interactions.