GSE129646
Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain [ATACseq]
Breast cancer metastasis is the leading cause of breast cancer-related mortalities in women. Differential gene expression programs enriched in the primary tumor is able to distinguish patients that experience relapse to different organs. Epigenomic changes often underlie transcriptomic differences and give rise to stable phenotypes. However, the epigenomic differences present in organotropic metastasis remains underexplored. Here we profile the active chromatin landscape of the claudin-low cell line MDA-MB-231 and its metastatic subpopulations that preferentially grow in the brain (BrM2), and lung (LM2). We find that metastatic cells harbor increased promoter and enhancer activation. Using ATAC-seq, we also define transcription factors that are enriched in an organotropic manner. Chromatin accessibility of metastatic cells correlates with shorter progression-free survival and is enriched in patients who have more aggressive subtypes of breast cancer. Overall design: RNAseq, ChIPseq (H3K4me3, H3K27ac) and ATACseq of MDA-MB-231 Par, LM2, and BrM2 cell lines