Extended Data Fig. 1: KMT2A N-terminus and C-terminus specific antibodies for AutoCUT&RUN chromatin profiling.

a, Pearson correlation matrices between KMT2A N-terminus and C-terminus specific antibodies over the merged KMT2A peaks for each sample. In the control CD34 + progenitors, as well as K562 and H1 cells signals for the KMT2A-N1 antibody (Millipore Cat# 05-764), KMT2A-N2 antibody (Cell Signaling Tech Cat# 14689 S), KMT2A-C1 antibody (Millipore Cat# 05-765) and KMT2A-C2 antibody (Santa Cruz Cat# sc-374392) are all highly correlated, indicating that the N-terminal and C-terminal regions of wild-type KMT2A co-localize on chromatin. In the KMT2Ar sample profiles the N-terminal antibodies show higher correlations with one another than they do with the C-terminal antibodies, indicating the KMT2A fusion binding is detected by the N-terminal antibodies and uncoupled from the KMT2A wild-type protein mapped by the C-terminal antibodies. b, Genome browser tracks showing wild-type KMT2A enrichment over the TSS of the EIF4E gene in both H1 and K562 cells. In contrast to CD34 + HSPCs, many critical hematopoietic cell fate determinants (for example HOXA9) are not bound by wild-type KMT2A in H1 or K562 cells. A broad distribution of KMT2A signal is found across the gene bodies of a limited collection of target genes (for example FAM78A) in K562 cells. Black scale bars = 10 kb. c, The Pearson correlation of KMT2A N- versus C-terminal profiles is significantly higher in the control KMT2A wild-type samples than in the KMT2Ar samples. Center line = median; box limits = first and third quartiles; whiskers show all data within 1.5 IQRs of the lower and upper quartiles; outliers are not shown; P value was computed using a two sample t-test (two-sided); wildtype, n = 12; KMT2Ar, n = 48.