Pharmacological modulation of H3K9me2 deposition in human colorectal cancer cells and transformed ES cells

Transformed variant of H9 human ES cells (t-hESC) represent a surrogate model for cancer stem cells in adherent cultures, which faithfully recapitulate the main functional, transcriptional, and epigenetic characteristics of CSCs in culture and in vivo. The use of G9a inhibitor BIX-01294 reduced the levels of H3K9me2 and global DNA methylation in t-hESCs. Thus, we performed transcriptome-profiling experiments on control and BIX-treated t-hESC to study the impact of G9a inhibition on gene networks associated with neoplastic stemness. Moreover, using a phenotypic chemical screening assay, we identified vanoxerine (VXN) as a new small molecule decreasing H3K9me2 deposition in t-hESCs. In addition to t-hESCs, transcriptome profiling was performed on colorectal cancer cell line HT29 upon treatment with VXN. In addition to annotaded genes, the analysis included the quantification of human retrotransposable elements. RNA-seq transcriptome profiling, HT29 and t-hESC human cell line. 2 biological replicates of each condition.