Fig. 4

Epigenetic variability is modulated by the hypoxic microenvironment. a FACS sorted EpCAM+ and HIF1α+ double-positive cells from the same mouse breast tumor; three groups of HIF1α staining were assigned, HIF1α negative (n = 762), HIF1α low (n = 139), HIF1α high (n = 55) (right plot). b Ranking of transcription factor motif variability of different HIF1α-staining groups, HIF1α negative (n = 702), HIF1α low (n = 95), HIF1α high (n = 42). c Examples of TF motif deviations, which significantly change in HIF1α high group compared with the others. In each comparison, HIF1α negative (n = 702), HIF1α low (n = 95), HIF1α high (n = 42). Significance of Wilcoxon test shown with n.s. (not significant), *p < 0.05 and **p < 0.01. d Flow cytometry analysis of HIF1α protein abundance in 4T1 breast cancer cells cultured in 5% oxygen (Ctrl, gray) or 1% oxygen for indicated time points. e Chromatin accessibility changes of hypoxic conditions compared with control. Red indicates higher, blue lower accessibility. f TF deviation examples of motifs whose accessibility increases in hypoxia over time in 4T1 breast cancer cells (TF deviation was calculated using ChromVAR)