Metabolic adaptations underlie epigenetic vulnerabilities in chemoresistant breast cancer. [ChIP-Seq]

Purpose:Assess the reprogramming of H3K4me1, H3K4me3, H3K27ac and H3K27me3 in paclitaxel-resistant triple-negative breast cancer cells relative to paclitaxel-sensitive cells Methods: ChIP-seq was performed on paclitaxel-treated MDA-MB-436 cells that are resistant to Paclitaxel (R20A, R20B, R20C) and in control-treated (DMSO) parental MDA-MB-436 cells that are sensitive to Paclitaxel (DMSO) Results: Using we mapped about 20 million sequence reads per sample to the human genome (hg19) and identified significant peaks in each cell lines using MACS.2.0 tool. Conclusions: Our study identified major reprogramming of H3K27me3 in the taxol-resistant TNBC cells relative to parental (TNBC cells), with loss of discrete H3K27me3 peaks in the resistant cells concomittent to acquisition of clusters of H3K27me3. Overall design: ChIP-seq was performed on paclitaxel-treated MDA-MB-436 cells that are resistant to Paclitaxel (R20A, R20B, R20C) and in control-treated (DMSO) parental MDA-MB-436 cells that are sensitive to Paclitaxel (DMSO)

研究目的：相较于紫杉醇敏感型细胞，本研究旨在探究紫杉醇耐药三阴性乳腺癌（triple-negative breast cancer, TNBC）细胞中H3K4me1、H3K4me3、H3K27ac及H3K27me3的重编程情况。
实验方法：对经紫杉醇处理的紫杉醇耐药MDA-MB-436细胞（R20A、R20B、R20C）以及经对照处理（二甲基亚砜，dimethyl sulfoxide, DMSO）的亲本紫杉醇敏感型MDA-MB-436细胞（DMSO组）开展染色质免疫共沉淀测序（Chromatin Immunoprecipitation sequencing, ChIP-seq）。
实验结果：我们将每个样本约2000万条序列读段比对至人类基因组（hg19），并通过MACS 2.0工具在各细胞系中鉴定出显著的结合峰。
研究结论：本研究发现，相较于亲本三阴性乳腺癌细胞，紫杉醇耐药三阴性乳腺癌细胞中H3K27me3发生了显著重编程：耐药细胞中原有的离散H3K27me3结合峰消失，同时获得了H3K27me3富集簇。
实验整体设计：对经紫杉醇处理的紫杉醇耐药MDA-MB-436细胞（R20A、R20B、R20C）以及经对照处理（二甲基亚砜，dimethyl sulfoxide, DMSO）的亲本紫杉醇敏感型MDA-MB-436细胞（DMSO组）进行染色质免疫共沉淀测序（Chromatin Immunoprecipitation sequencing, ChIP-seq）。