PT  - JOURNAL ARTICLE
AU  - Derek H. Janssens
AU  - Michael P. Meers
AU  - Steven J. Wu
AU  - Ekaterina Babaeva
AU  - Soheil Meshinchi
AU  - Jay F. Sarthy
AU  - Kami Ahmad
AU  - Steven Henikoff
TI  - Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia
AID  - 10.1101/2020.10.06.328948
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.10.06.328948
4099  - http://biorxiv.org/content/early/2021/03/10/2020.10.06.328948.short
4100  - http://biorxiv.org/content/early/2021/03/10/2020.10.06.328948.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.