Arima Genomics: Transposable elements reorganise the 3D genome structure in CDK4/6 inhibitors resistant breast cancer

Transposable elements (TEs) hold regulatory functions in cancer cells by promoting oncogenic gene expression. Here, we identified and characterized regulatory TEs in patient-derived xenograft (PDX) models of acquired CDK4/6i resistance in ER+ breast cancer. We found that loss of DNA methylation results in transcriptional reactivation of TEs in CDK4/6i resistance. These reactivated TEs are enriched for enhancer signatures and transcription factor binding, including CTCF. Using chromosome conformation capture (Hi-C and Capture Hi-C) experiments, we show that regulatory TEs contribute to the formation of new 3D chromatin interactions, which contact and regulate expression of distal genes. Together, we demonstrate that TEs are hijacked by transcription factors to alter the 3D genome structure in CDK4/6i resistant breast cancer.