Project description:We have recently discovered a class of anti-cancer agents, curaxins, which suppress transcription of oncogenes. Here we demonstrate that curaxins preferentially downregulate expression of genes controlled by enhancers and super-enhancers via interrupting enhancer/promoter spatial communication. Our observations made both on a model of enhancer-regulated transcription of chromatinized template and on cultured cancer cells allow classifying curaxins as a novel type of epigenetic drugs that target the 3D genome organization.
Project description:We have recently discovered a class of anti-cancer agents, curaxins, which suppress transcription of oncogenes. Here we demonstrate that curaxins preferentially downregulate expression of genes controlled by enhancers and super-enhancers via interrupting enhancer/promoter spatial communication. Our observations made both on a model of enhancer-regulated transcription of chromatinized template and on cultured cancer cells allow classifying curaxins as a novel type of epigenetic drugs that target the 3D genome organization.
Project description:Recently we characterized a class of anti-cancer agents (curaxins) that disturbs DNA/histone interactions within nucleosomes. Here, using a combination of genomic and in vitro approaches, we demonstrate that curaxins strongly affect spatial genome organization and compromise enhancer-promoter communication, which is necessary for the expression of several oncogenes, including MYC. We further show that curaxins selectively inhibit enhancer-regulated transcription of chromatinized templates in cell-free conditions. Genomic studies also suggest that curaxins induce partial depletion of CTCF from its binding sites, which contributes to the observed changes in genome topology. Thus, curaxins can be classified as epigenetic drugs that target the 3D genome organization.
