Year: 2019
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1010591873, G1012269920, Mechanism of yFACT Action during Chromatin Transcription, Mechanisms of PARP-1 interaction with chromatin, G2934504215, G325520570, Modulation of cancer specific transcriptional factors with small molecules, G6436465170, G6634403258, G7213441469, Roswell Park Cancer Center Support Grant
OpenAlex ID: W2933301484