...
首页> 外文期刊>Scientific reports. >Utilization of NGS technologies to investigate transcriptomic and epigenomic mechanisms in trastuzumab resistance
【24h】

Utilization of NGS technologies to investigate transcriptomic and epigenomic mechanisms in trastuzumab resistance

机译:NGS技术利用NGS技术探讨曲妥珠珠抵抗的转录组和外形组织机制

获取原文
           

摘要

NGS (Next Generation Sequencing) technologies allows us to determine key gene expression signaturesthat correlate with resistance (and responsiveness) to anti-cancer therapeutics. We have undertakena transcriptomic and chromatin immunoprecipitation followed by sequencing (ChIP-seq) approachto describe diferences in gene expression and the underlying chromatin landscape between tworepresentative HER2+ cell lines, one of which is sensitive (SKBR3) and the other which is resistant(JIMT1) to trastuzumab. We identifed diferentially expressed genes (DEGs) and diferentiallyexpressed transcripts (DETs) between SKBR3 and JIMT1 cells. Several of the DEGs are components ofthe Polycomb Repressing Complex 2 (PRC2), and they are expressed higher in JIMT1 cells. In addition,we utilized ChIP-seq to identify H3K18ac, H3K27ac and H3K27me3 histone modifcations genomewide.We identifed key diferences of H3K18ac and H3K27ac enrichment in regulatory regions, found acorrelation between these modifcations and diferential gene expression and identifed a transcriptionfactor binding motif for LRF near these modifcations in both cell lines. Lastly, we found a smallsubset of genes that contain repressive H3K27me3 marks near the gene body in SKBR3 cells but areabsent in JIMT1. Taken together, our data suggests that diferential gene expression and trastuzumabresponsiveness in JIMT1 and SKBR3 is determined by epigenetic mechanisms.
机译:NGS(下一代测序)技术使我们能够确定关键基因表达签名与抗癌治疗剂的抗性(和反应性)相关。我们已经进行了转录组和染色质免疫沉淀,然后进行测序(芯片-SEQ)方法描述基因表达中的差异和逆住HER2 +细胞系之间的底层染色质横向,其中一个是敏感(SKBR3),另一个是抗性(JIMT1)的另一个Trastuzumab。我们在SKBR3和JIMT1细胞之间识别不同表达的基因(DEGS)和不同的转录转录物(DEDs)。几个Deg是Polycomb抑制复合物2(PRC2)的组分,它们在JIMT1细胞中表达较高。此外,我们利用芯片SEQ鉴定H3K18AC,H3K27AC和H3K27ME3组蛋白改性.WE鉴定了调节区H3K18AC和H3K27Ac富集的关键差异,发现这些修饰和差异基因表达之间的疾病,并鉴定了LRF附近的转录物料结合基序。这些修改在两种细胞系中。最后,我们发现了一种小型基因,其含有在Skbr3细胞基因体附近的压制H3K27ME3标记,而是在JimT1中的面积。我们的数据结合在一起,表明JIMT1和SKBR3中的差异基因表达和曲据抑制性通过表观遗传机制决定。

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