An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions.
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Authors
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
Peña-Rømer, I
Lorenzini, E
Koche, R
Zhan, Y
Shliaha, PV
Cooper, AJ
Fan, Z
Shlyueva, D
Johansen, JV
Hendrickson, RC
Helin, K
Document Type
Journal Article
Date
2023-12-11
Date Accepted
2023-11-03
Abstract
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.
Citation
EMBO Journal, 2023, 42 (24), pp. e114221 -
Source Title
EMBO Journal
Publisher
SPRINGERNATURE
ISSN
0261-4189
eISSN
1460-2075
1460-2075
1460-2075
Collections
Research Team
Chromatin Biology
CEO Office
CEO Office