An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions Journal Article
| Authors: | Radzisheuskaya, A.; Peña-Rømer, I.; Lorenzini, E.; Koche, R.; Zhan, Y.; Shliaha, P. V.; Cooper, A. J.; Fan, Z.; Shlyueva, D.; Johansen, J. V.; Hendrickson, R. C.; Helin, K. |
| Article Title: | An alternative NURF 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 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. |
| Keywords: | controlled study; unclassified drug; human cell; genetics; leukemia, myeloid, acute; pathogenesis; nonhuman; protein domain; mouse; metabolism; animal tissue; cell survival; cell growth; protein protein interaction; animal experiment; animal model; transcription factor; in vivo study; in vitro study; transcription factors; chromatin; adenosine triphosphatase; drosophila proteins; chromatin assembly and disassembly; drosophila protein; acute myeloid leukemia; insulator element; nucleosome remodeling factor; transcription factor ctcf; chromatin remodeling; humans; human; male; female; article; clustered regularly interspaced short palindromic repeat; acute myeloid leukemia cell line; bptf; insulator regions; smarca5; bptf associated protein 18; swi snf related matrix associated actin dependent regulator of chromatin subfamily a5 |
| Journal Title: | EMBO Journal |
| Volume: | 42 |
| Issue: | 24 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-12-11 |
| Start Page: | e114221 |
| Language: | English |
| DOI: | 10.15252/embj.2023114221 |
| PUBMED: | 37987160 |
| PROVIDER: | scopus |
| PMCID: | PMC10711654 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF -- Source: Scopus |
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