An Ikaros-Containing Chromatin-Remodeling Complex in Adult-Type Erythroid Cells
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We have previously described a SWI/SNF-related protein complex (PYR complex) that is restricted to definitive (adult-type) hematopoietic cells and that specifically binds DNA sequences containing long stretches of pyrimidines. Deletion of an intergenic DNA-binding site for this complex from a human beta-globin locus construct results in delayed human gamma- to beta-globin switching in transgenic mice, suggesting that the PYR complex acts to facilitate the switch. We now show that PYR complex DNA-binding activity also copurifies with subunits of a second type of chromatin-remodeling complex, nucleosome-remodeling deacetylase (NuRD), that has been shown to have both nucleosome-remodeling and histone deacetylase activities. Gel supershift assays using antibodies to the ATPase-helicase subunit of the NuRD complex, Mi-2 (CHD4), confirm that Mi-2 is a component of the PYR complex. In addition, we show that the hematopoietic cell-restricted zinc finger protein Ikaros copurifies with PYR complex DNA-binding activity and that antibodies to Ikaros also supershift the complex. We also show that NuRD and SWI/SNF components coimmunopurify with each other as well as with Ikaros. Competition gel shift experiments using partially purified PYR complex and recombinant Ikaros protein indicate that Ikaros functions as a DNA-binding subunit of the PYR complex. Our results suggest that Ikaros targets two types of chromatin-remodeling factors-activators (SWI/SNF) and repressors (NuRD)-in a single complex (PYR complex) to the beta-globin locus in adult erythroid cells. At the time of the switch from fetal to adult globin production, the PYR complex is assembled and may function to repress gamma-globin gene expression and facilitate gamma- to beta-globin switching.
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IKZF1 behaves promiscuously, interacting with both activator and repressor chromatin-remodeling complexes.
“interestingly, iKZF1 behaves in a promiscuous manner, interacting with both activator and repressor chromatin-remodeling complexes (Kim et al. 1999;O'Neill et al. 2000).”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as O'Neill et al. 2000
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Cites
Ikaros DNA-Binding Proteins Direct Formation of Chromatin Remodeling Complexes in Lymphocytes
Kim, J., Sif, S., Jones, B., Jackson, A., Koipally, J., Heller, E., Winandy, S., Viel, A., Sawyer, A., Ikeda, T., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80034-5 · Cited by 587 · see citing works
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ATP-dependent chromatin remodeling: genetics, genomics and mechanisms
Hargreaves, D. C., & Crabtree, G. R. (2011) · Cell Research · doi:10.1038/cr.2011.32 · Cited by 923 · see citing works
Zhang, T., Wang, Y.-F., Montoya, A., Patrascan, I., Nebioglu, N., Pallikonda, H. A., Georgieva, R., King, J. W. D., Kramer, H. B., Shliaha, P. V., et al. (2025) · Blood · doi:10.1182/blood.2024024787 · Cited by 14 · see citing works
From serendipity to strategy: molecular glue degraders in cancer therapeutics
Darling, S., Bajrami, I., & West, S. C. (2025) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2025.2564068 · Cited by 10 · see citing works
“…interestingly, iKZF1 behaves in a promiscuous manner, interacting with both activator and repressor chromatin-remodeling complexes (Kim et al. 1999; O’Neill et al. 2000). through this mechanism, iKZF1 – and its other family members – regulate cell-fate decisions during haematopoiesis, primarily in…”
- Authors
- O'Neill, D. W., Schoetz, S. S., Lopez, R. A., Castle, M., Rabinowitz, L., Shor, E., Krawchuk, D., Goll, M. G., Renz, M., Seelig, H.-P., Han, S., Seong, R. H., Park, S. D., Agalioti, T., Munshi, N., Thanos, D., Erdjument-Bromage, H., Tempst, P., & Bank, A.
- Affiliations
- Departments of Pathology
- Genetics and Development
- Karlsruhe Institute of Technology (DE)
- Seoul National University (KR)
- Biochemistry and Molecular Biophysics
- Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
- Memorial Sloan Kettering Cancer Center (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Bank, Arthur
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-10-15
- Volume
- 20
- Issue
- 20
- Pages
- 7572-7582
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC86310
- OpenAlex
- W2170927603
- Cited by
- 160
- References
- 1
- Citations by year
- 2025: 1 · 2024: 6 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 4 · 2014: 13 · 2013: 5 · 2012: 1
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P60HL028381, HL 28381)
- National Cancer Institute (P30CA008748)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 25274)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- Ikaros, chromatin remodeling, NuRD complex, SWI/SNF complex, definitive hematopoiesis, beta-globin locus, histone deacetylase, nucleosome remodeling, DNA-binding proteins, transcriptional repression, transcriptional activation
- MeSH terms
- Adenosine Triphosphatases, Aging, Animals, Autoantigens, Chromatin, DNA, DNA Helicases, DNA-Binding Proteins, Leukemia, Erythroblastic, Acute, Gene Expression Regulation, Globins, Histone Deacetylases, Histones, Humans, Mice, Transgenic, Nuclear Proteins, Precipitin Tests, Protein Binding, Substrate Specificity, Transcription Factors, Tumor Cells, Cultured, Zinc Fingers, Macromolecular Substances, Mice, Ikaros Transcription Factor, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Sin3 Histone Deacetylase and Corepressor Complex
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