Yu Feng, Shen Xingyong, Fan Li, Yu Zhaocai
Department of Medical Oncology, The People's Hospital of Shaanxi Province, Xi'an, P.R. China.
Department of Medical Oncology, Xijing Hospital, The Fourth Military Medical University, Xi'an, P.R. China.
Sci Rep. 2015 Dec 11;5:18100. doi: 10.1038/srep18100.
Human liver cancer is the cancer commonly seen clinically. The transcription of ribosomal DNA (rDNA) is a critical step for cells, and epigenetic marks such as post-translational histone modifications have been involved in the regulation of rDNA transcription. But less is known about the pathogenesis of the liver cancers concerning the rDNA transcription regulation. Here we aligned the ChIP-seq data of histone modification markers and CTCF to the human genome assembly which contains a single rDNA repeat in human liver cancer cell and validated their distribution with ChIP-QPCR. Human liver cancer cell possesses a higher enrichment of H3K4me1 and H3K27me3 at ~28 kb within the intergenic spacer (IGS) of rDNA and a higher enrichment of H3K4me3 and H3K27ac upstream of TSS. Furtherly, we studied whether UBF could affect histone modification markers and CTCF at rDNA in human liver cancer cell. UBF depletion leads to a decrease of gene activation mark H3K4me3 across the rDNA promoter. And other histone modification marks and CTCF were not altered after UBF depletion. Taken together, our data showed a high resolution map of histone modification marks at rDNA in human liver cancer cell and provide novel evidence to decipher chromatin-mediated regulation of rDNA in liver cancer.
人类肝癌是临床上常见的癌症。核糖体DNA(rDNA)的转录是细胞的关键步骤,并且诸如翻译后组蛋白修饰等表观遗传标记已参与rDNA转录的调控。但是,关于肝癌在rDNA转录调控方面的发病机制,人们了解较少。在此,我们将组蛋白修饰标记和CTCF的ChIP-seq数据与人类基因组组装进行比对,该组装在人类肝癌细胞中包含单个rDNA重复序列,并通过ChIP-QPCR验证了它们的分布。人类肝癌细胞在rDNA基因间隔区(IGS)内约28 kb处具有较高的H3K4me1和H3K27me3富集,在转录起始位点(TSS)上游具有较高的H3K4me3和H3K27ac富集。此外,我们研究了上游结合因子(UBF)是否会影响人类肝癌细胞中rDNA处的组蛋白修饰标记和CTCF。UBF缺失导致rDNA启动子上基因激活标记H3K4me3减少。UBF缺失后,其他组蛋白修饰标记和CTCF未发生改变。综上所述,我们的数据显示了人类肝癌细胞中rDNA处组蛋白修饰标记的高分辨率图谱,并为解读肝癌中染色质介导的rDNA调控提供了新证据。