The alternative Nucleosome Remodeling Factor complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions (ATAC-seq)

Efficient treatment of Acute Myeloid Leukemia (AML) patients remains a challenge despite recent advances. Here using a CRISPRi screen targeting chromatin factors, we identified BPTF as an essential regulator of AML cell survival. We demonstrate that BPTF forms an alternative NURF chromatin remodeling complex with SMARCA5 and BAP18, which regulates the accessibility of a large set of insulator regions in leukemic cells. This ensures efficient CTCF binding and boundary formation between topologically associated domains that is essential for maintaining the leukemic transcriptional programs. We also demonstrate that the well-studied PHD2-BROMO chromatin reader modules of BPTF are dispensable for leukemic cell growth. Taken together, our results uncover how the alternative NURF complex contributes to leukemia and provide a rationale for its targeting in AML. 2 ATAC-sequencing experiments; the negative controls for each set are clearly specified in the title. Experiment 1: assessing the effect of BPTF KO on chromatin accessibility. Experiment 2: assessing the effect of SMARCA5 KO on chromatin accessibility. 2 biological replicates per sample were used. Experiment 3: ATAC-sequencing experiment assessing the effect of rapid SMARCA5 degradation on chromatin accessibility. 2 biological replicates per sample were used. The cells were treated with DMSO or dTAG-V1, as indicated in the sample name.