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The alternative Nucleosome Remodeling Factor complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions

ABSTRACT: 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, while contributing to complex recruitment to chromatin, 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Pavel Shliaha

LAB HEAD: Pavel Shliaha

PROVIDER: PXD044656 | Pride | 2023-11-12

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	2020_03_15_BPTF_3rd_all_IP_proteins.csv	Csv
	2020_03_15_BPTF_3rd_enriched_IP_proteins.csv	Csv
	BPTF_Fr0.pdResult	Other
	BPTF_Fr01.raw	Raw
	BPTF_Fr02.raw	Raw

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