An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions.

Autor: Radzisheuskaya A; Division of Cancer Biology, The Institute of Cancer Research, London, UK.; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark.; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Peña-Rømer I; Division of Cancer Biology, The Institute of Cancer Research, London, UK.; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark., Lorenzini E; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark., Koche R; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Zhan Y; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Shliaha PV; Microchemistry & Proteomics Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Cooper AJ; Division of Cancer Biology, The Institute of Cancer Research, London, UK., Fan Z; Division of Cancer Biology, The Institute of Cancer Research, London, UK.; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark., Shlyueva D; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark.; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Johansen JV; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark., Hendrickson RC; Microchemistry & Proteomics Core, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Helin K; Division of Cancer Biology, The Institute of Cancer Research, London, UK.; Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.; The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of Copenhagen, Copenhagen, Denmark.; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2023 Dec 11; Vol. 42 (24), pp. e114221. Date of Electronic Publication: 2023 Nov 21.
DOI: 10.15252/embj.2023114221
Abstrakt: 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.
(© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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