Selective advantage of epigenetically disrupted cancer cells via phenotypic inertia [ATAC-Seq]

Mutations in over one hundred genes, belonging to diverse classes of epigenetic regulators, resulted in significant fitness advantage under nutrient starvation and acidic conditions, suggesting that disruption of epigenetic control, at multiple levels of the regulatory network, promotes broad resistance of cells to stressful environments. To uncover the molecular mechanisms of such phenomenon, and to understand how loss of epigenetic regulators gives advantage during stress, we examined how chromatin accessibility changes in nutrient-deprived conditions using ATAC-seq. ATAC-seq analysis of melanoma cells expressing 4-7sgRNAs targeting members of the PRC2 complex (EED, EZH2, SUZ12), histone H1B (HIST1H1B), the chromatin remodeller SMARCD1 and a non-expressed control gene (TNP2), and grown in either unperturbed conditions (d0) or under glutamine deprivation (d2). Overall design: Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) for TNP2, EED, EZH2, SUZ12, HIST1H1B and SMARCD1 KO cells