Nanoscale Visualization of the Chromatin Remodeling as Potent Biomarker in Aggressive Breast Cancers

Abstract Chromatin organization, predominantly histone modifications is crucial to regulating gene expression. Genomic instability caused by the aberrant chromatin structure leads to various cancer subtypes. However, genome-wide higher-order structures of euchromatin and heterochromatin and understanding their dynamical ratio concerning cancer are poorly characterized. Here, utilizing super-resolution microscopy, we studied the remodelling structural aspects of euchromatin and heterochromatin in various cancer subtypes including the most aggressive triple-negative breast cancer (TNBC) lacking targeted therapies and is difficult to diagnose. The nanoscopic visualization revealed a prominent reorganization of euchromatin and heterochromatin ratios and a distinct spatial distribution of chromatin domains among breast cancer subtypes with a special emphasis on the TNBC and HER-2 positive. Increased expression of remodelling protein SSRP-1 supports the structural changes of chromatin in all breast cancer cells. These observations, contemplate the possibility of euchromatin and heterochromatin domain ratios in predicting and understanding the breast cancer subtypes and can be targeted for personalized cancer therapy.