Profiling of Lsd1 and chromatin marks in epithelial cells overexpressing HOTAIR variants

Epithelial-to-mesenchymal transitions (EMT) underlie a loss of epithelial traits by normal cells during development and neoplastic cells during cancer metastasis. The long noncoding RNA HOTAIR triggers EMT, in part by serving as a scaffold for Polycomb Repressive Complex 2 (PRC2) and thus promoting repressive histone H3 Lys27 methylation. In addition to PRC2, HOTAIR interacts with the Lsd1 lysine demethylase, an epigenetic regulator of cell fate during development and differentiation. Here, we showed that HOTAIR requires the Lsd1-interacting domain, but not the PRC2-interacting domain, to promote migration of epithelial cells. Our results suggest that the HOTAIR-Lsd1 asociation redistributes Lsd1 on chromatin and hence reprograms the epithelial transcriptome. The experiment was performed in biological duplicates for each cell line following the protocol of CUT&RUN (Skene et al 2018). Immunoprecipitated DNA was sequenced.