Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes.
Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes.
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DOI：
10.1186/s12864-018-4533-0
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发表时间：
2018-02-20
期刊：
影响因子：
4.4
通讯作者：
Dent SYR
中科院分区：
文献类型：
--
作者：
Xi Y;Shi J;Li W;Tanaka K;Allton KL;Richardson D;Li J;Franco HL;Nagari A;Malladi VS;Coletta LD;Simper MS;Keyomarsi K;Shen J;Bedford MT;Shi X;Barton MC;Kraus WL;Li W;Dent SYR
表观遗传调控因子在多种癌症中经常发生突变或异常表达，导致转录状态改变，从而导致细胞身份、行为和对治疗的反应发生变化。为了确定乳腺癌表观遗传格局的改变，我们通过ChIP-Seq分析了8个关键组蛋白修饰的分布，以及原发性（GRO-seq）和稳态（RNA-Seq）转录组在13个不同细胞系中的分布，这些细胞系代表了乳腺癌和永生化人乳腺上皮细胞的5种分子亚型。利用不同组蛋白修饰信号的组合模式，我们定义了亚型特异性染色质特征来命名潜在的生物标志物。该方法确定了AFAP1-AS1是与细胞增殖和上皮-间质转化相关的三阴性乳腺癌特异性基因。此外，我们在基础TNBC细胞系中的染色质定位数据与TCGA中的基因表达模式一致，表明雄激素受体途径的活性降低，而维生素D生物合成途径的活性增加。总之，这些数据集为组蛋白修饰谱提供了一个全面的资源，这些组蛋白修饰谱定义了表观遗传景观，揭示了乳腺癌细胞系亚型的关键染色质特征，有可能确定新的和可操作的治疗靶点。本文的在线版本（10.1186/s12864-018-4533-0）包含补充内容，仅供授权用户使用。
Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy. To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells. Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway. Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment. The online version of this article (10.1186/s12864-018-4533-0) contains supplementary material, which is available to authorized users.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
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期刊：
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影响因子：
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Rosenbloom KR;Dreszer TR;Pheasant M;Barber GP;Meyer LR;Pohl A;Raney BJ;Wang T;Hinrichs AS;Zweig AS;Fujita PA;Learned K;Rhead B;Smith KE;Kuhn RM;Karolchik D;Haussler D;Kent WJ
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发表时间：
2016-07
期刊：
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
影响因子：
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