AP-1 dependent changes in chromatin accessibility in resistant basal cell carcinoma cell line

Tumor heterogeneity and lack of knowledge about resistant cell states remain a significant barrier to effective targeted cancer therapies. Basal cell carcinomas (BCCs) uniformly depend on Hedgehog (Hh)/Gli signaling for cell growth. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies Gli1 activity, but nMRTF cell state and key factors driving its accumulation remain unknown. We have determined that AP-1 transcription factor activity is essential to maintain MRTF activation. Here, we treat a murine BCC cell line with small molecule AP-1 inhibitor and analyze chromatin accessibility profiles. ASZ001 cells were plated and serum-starved with or without 20 uM of AP-1 inhibitor T-5224 for 24 hours, then processed for ATAC-seq. Two biological replicates were sequenced per treatment group.