Cancer chromatin signatures – role of histone variants
Epigenetic modifications contribute to the establishment and maintenance of cancer. Whether histone variants contribute to these transformations is not known.We investigated the relative expression levels of histone macroH2A1 splice variants at the mRNA and protein levels in breast cancer cells and tumor samples. We determined that differential expression of macroH2A1 variants correlate with intrinsic molecular subclasses of breast cancer and molecular characteristics of Epithelial-Mesenchymal Transition (EMT). We found increased macroH2A1.1/macroH2A1 mRNA ratios to be associated with the claudin-low intrinsic subtype in breast cancer cell lines. Clinically, untreated Triple Negative Breast Cancers presenting a high macroH2A1.1 mRNA ratio exhibit a poor outcome. At the molecular level this association translates into a positive correlation between macroH2A1ratios and molecular characteristics of the EMT process.Our hypothesis is that specific cellular phenotypes during the EMT process relate to nuclear localization of macroH2A1.1.