An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions.
Date
2023-12-11Author
Radzisheuskaya, A
Peña-Rømer, I
Lorenzini, E
Koche, R
Zhan, Y
Shliaha, PV
Cooper, AJ
Fan, Z
Shlyueva, D
Johansen, JV
Hendrickson, RC
Helin, K
Type
Journal Article
Metadata
Show full item recordAbstract
Efficient treatment of acute myeloid leukemia (AML) patients remains a challenge despite recent therapeutic advances. Here, using a CRISPRi screen targeting chromatin factors, we identified the nucleosome-remodeling factor (NURF) subunit 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 domains 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.
Collections
Subject
BPTF
SMARCA5
acute myeloid leukemia
chromatin remodeling
insulator regions
Humans
Chromatin
Transcription Factors
Leukemia, Myeloid, Acute
Drosophila Proteins
Chromatin Assembly and Disassembly
Research team
Chromatin Biology
CEO Office
Language
eng
Date accepted
2023-11-03
License start date
2023-12-11
Citation
EMBO Journal, 2023, 42 (24), pp. e114221 -
Publisher
WILEY