The anti-cancer drugs curaxins target spatial genome organization.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30926878.
- Also identified by DOI 10.1038/s41467-019-09500-7 and PMC identifier 6441033.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.
Medical subject headings
- Antineoplastic Agents
- Carbazoles
- Genome, Human