Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes

Yuanxin Xi, Jiejun Shi, Wenqian Li, Kaori Tanaka, Kendra L. Allton, Dana Richardson, Jing Li, Hector L. Franco, Anusha Nagari, Venkat S. Malladi, Luis Della Coletta, Melissa S. Simper, Khandan Keyomarsi, Jianjun Shen, Mark T. Bedford, Xiaobing Shi, Michelle C. Barton, W. Lee Kraus, Wei Li, Sharon Y. R. Dent

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.