• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Epigenetics & Chromatin >Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia
【24h】

Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia

机译：ChIP-seq数据的定量分析揭示了缺氧条件下癌细胞中动态和持续的H3K4me3和H3K27me3调节

获取原文
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background A comprehensive assessment of the epigenetic dynamics in cancer cells is the key to understanding the molecular mechanisms underlying cancer and to improving cancer diagnostics, prognostics and treatment. By combining genome-wide ChIP-seq epigenomics and microarray transcriptomics, we studied the effects of oxygen deprivation and subsequent reoxygenation on histone 3 trimethylation of lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in a breast cancer cell line, serving as a model for abnormal oxygenation in solid tumors. A priori, epigenetic markings and gene expression levels not only are expected to vary greatly between hypoxic and normoxic conditions, but also display a large degree of heterogeneity across the cell population. Where traditionally ChIP-seq data are often treated as dichotomous data, the model and experiment here necessitate a quantitative, data-driven analysis of both datasets. Results We first identified genomic regions with sustained epigenetic markings, which provided a sample-specific reference enabling quantitative ChIP-seq data analysis. Sustained H3K27me3 marking was located around centromeres and intergenic regions, while sustained H3K4me3 marking is associated with genes involved in RNA binding, translation and protein transport and localization. Dynamic marking with both H3K4me3 and H3K27me3 (hypoxia-induced bivalency) was found in CpG-rich regions at loci encoding factors that control developmental processes, congruent with observations in embryonic stem cells. Conclusions In silico -identified epigenetically sustained and dynamic genomic regions were confirmed through ChIP-PCR in vitro, and obtained results are corroborated by published data and current insights regarding epigenetic regulation.
机译：背景技术对癌细胞中表观遗传动力学的全面评估是了解癌症潜在分子机制以及改善癌症诊断，预后和治疗的关键。通过结合全基因组ChIP-seq表观基因组学和微阵列转录组学，我们研究了氧剥夺和随后的再加氧对乳腺癌细胞系中赖氨酸4（H3K4me3）和赖氨酸27（H3K27me3）的组蛋白3三甲基化的影响，作为模型用于实体瘤中的异常氧合。先验的，表观遗传的标记和基因表达水平不仅预期在低氧和常氧条件之间有很大的不同，而且在整个细胞群体中表现出很大程度的异质性。传统上将ChIP-seq数据通常视为二分数据，此处的模型和实验需要对两个数据集进行定量的，数据驱动的分析。结果我们首先鉴定了具有持续表观遗传标记的基因组区域，从而为特定样品提供了参考，从而可以进行定量ChIP-seq数据分析。持续的H3K27me3标记位于着丝粒和基因间区域附近，而持续的H3K4me3标记与参与RNA结合，翻译，蛋白质转运和定位的基因有关。 H3K4me3和H3K27me3（缺氧诱导的双价）的动态标记是在控制发育过程的基因座编码因子的富含CpG的区域中发现的，与胚胎干细胞的观察结果一致。结论在体外通过ChIP-PCR证实了在计算机上鉴定的表观遗传学上持续的和动态的基因组区域，获得的结果得到了已发表的数据和有关表观遗传调控的最新见解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号