EZH2 binds transcripts for splicing regulation and redistribution of H3K27me3 and H3K36me3 in prostate cancer cells. Homo sapiens

PRC2 was found to bind to various RNAs, both noncoding RNA, coding RNA and nascent transcription RNA in ESCs. In order to determine the RNA binding profile and the binding characteristic in prostate cancer cells, through RIP-seq, we found out that EZH2 could associate with nascent transcripts in prostate cancer cells which have profound influence on the transcript splicing. What is more, we found that the H3K36me3 and H3K27me3 distribution in gene body region were regulated by EZH2 association with nascent transcripts. Overall design: RIP-seq, ChIP-seq and RNA-seq was performed in androgen-dependent prostate cancer cells LNCaP (AD) and androgen-independent prostate cancer cells LNCaP (AI).

研究证实，多梳抑制复合体2（PRC2）可结合胚胎干细胞（ESCs）中的多种RNA，涵盖非编码RNA、编码RNA及新生转录RNA。为探明前列腺癌细胞内的RNA结合谱与结合特性，本研究通过RNA免疫沉淀测序（RIP-seq）分析发现，zeste增强子同源物2（EZH2）可与前列腺癌细胞中的新生转录本相结合，且该结合对转录本剪接具有显著影响。此外，本研究还发现，基因体区域内的组蛋白H3赖氨酸36三甲基化（H3K36me3）与组蛋白H3赖氨酸27三甲基化（H3K27me3）的分布模式，可通过EZH2与新生转录本的结合受到调控。实验设计概述：本研究对雄激素依赖型前列腺癌细胞系LNCaP（AD）与非雄激素依赖型前列腺癌细胞系LNCaP（AI），分别开展了RNA免疫沉淀测序（RIP-seq）、染色质免疫沉淀测序（ChIP-seq）及RNA测序（RNA-seq）实验。