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bioRxiv · 10.1101/2020.10.06.328948

Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia

Janssens, D.·Meers, M. P.·Wu, S. J.·Babaeva, E.·Meshinchi, S.·Sarthy, J. F.·Ahmad, K.·Henikoff, S.
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Abstract

Acute myeloid and lymphoid leukemias often harbor chromosomal translocations involving the Mixed Lineage Leukemia-1 gene, encoding the KMT2A lysine methyltransferase. The most common translocations produce in-frame fusions of KMT2A to other chromatin regulatory proteins. Here we develop a strategy to map the genome-wide occupancy of oncogenic KMT2A fusion proteins in primary patient samples regardless of fusion partner. By modifying the versatile CUT&Tag method for full automation we identify common and tumor-specific patterns of aberrant chromatin regulation induced by different KMT2A fusion proteins. Integration of automated and single-cell CUT&Tag uncovers epigenomic heterogeneity within patient samples and predicts sensitivity to therapeutic agents.

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Janssens, D., Meers, M. P., Wu, S. J., Babaeva, E., Meshinchi, S., Sarthy, J. F., Ahmad, K., Henikoff, S.. 2020-10-08. Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia. https://doi.org/10.1101/2020.10.06.328948

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