Development of a HT-ATACseq assay to identify epigenetic regulators of Ewing Sarcoma cancer cells (Chemical Biology Consortium/NCI Experimental Therapeutics Collaboration)

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

During this period, the project team has worked towards developing a target agnostic small molecule screening technology that exploits tumor-specific chromatin accessibility states as a relevant and direct functional readout. By targeting chromatin accessibility instead of a single transcription factor or chromatin regulatory protein, the limitations associated with in vitro screening and single protein target identification can be overcome. The project team has focused on optimizing experimental conditions towards a high throughput screening platform capable of measuring dynamic states of chromatin accessibility in cells using an enzyme-based approach, Assay for Transpose-Accessible Chromatin (ATAC). This screening technique represents a promising new paradigm in oncology drug discovery that will increase our mechanistic knowledge of tumor-specific changes in the epigenome and expand the repertoire of druggable targets. Applying this strategy, we will screen small molecule libraries assaying chromatin accessibility at regions specific for Ewing sarcoma.