An epic advance in epigenomics: Automated CUT&RUN enables chromatin profiling for scaled research & drug discovery applications

Dynamic changes in chromatin drive gene expression programs during cellular development and contribute to pathological changes underlying disease. To date, efforts to characterize chromatin dynamics have largely focused on chromatin accessibility (ATAC-seq) and DNA methylation profiling (bisulfite-seq). However, these assays provide a largely binary view of chromatin (open vs. closed), limiting their ability to decipher clear determinants of cellular identity or derive mechanistic insight into disease etiology. 

 

Epigenomic features – such as histone post-translational modifications (PTMs) and chromatin-associated proteins (e.g. transcription factors) – regulate chromatin structure, gene expression, and cell function. Mapping these features provides a rich context to study cell fate and offers the potential for discovering new biomarkers and drug targets. Despite widespread interest, efforts to integrate epigenomics into large-scale cell-type profiling and drug development pipelines have been hampered by the poor sensitivity, low throughput, and high costs of traditional chromatin mapping technology (ChIP-seq).

 

Here, we present a breakthrough automated CUT&RUN (autoCUT&RUN) assay for rapid, ultra-sensitive epigenomics. Our workflow generates reliable profiles down to 10,000 cells and is supported by rigorous optimization, high-quality antibodies, robust spike-in controls, and streamlined DNA cleanup using magnetic SPRI beads. This presentation will illustrate how autoCUT&RUN can be applied at-scale to map the epigenome in challenging clinical samples, detect dynamic changes after drug treatment, and identify cell-specific chromatin signatures. Our technology has broad applications in fields where the potential of epigenomics has yet to be fully realized, including cell identity fingerprinting and translational research.

 

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