Regulation of Chromatin Remodeling by Inositol Polyphosphates
Open accessAbstract
Chromatin remodeling is required for efficient transcription of eukaryotic genes. In a genetic selection for budding yeast mutants that were defective in induction of the phosphate-responsive PHO5 gene, we identified mutations in ARG82/IPK2 , which encodes a nuclear inositol polyphosphate kinase. In arg82 mutant strains, remodeling of PHO5 promoter chromatin is impaired, and the adenosine triphosphate–dependent chromatin-remodeling complexes SWI/SNF and INO80 are not efficiently recruited to phosphate-responsive promoters. These results suggest a role for the small molecule inositol polyphosphate in the regulation of chromatin remodeling and transcription.
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Several further studies have supported the importance of Arg82 kinase activity in transcriptional regulation and chromatin remodelling, together suggesting that Ins(1,4,5,6)P4 has an important regulatory role in yeast.
“Several further studies have supported the importance of Arg82 kinase activity in transcriptional regulation and chromatin remodelling 37-39, together suggesting that Ins(1,4,5,6)P4 has an important regulatory role in yeast.”
From Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate (2012) · cites this paper as [37]
The passage on the Arg82D131A mutant (section labeled Abstract; page unavailable) supports the importance of Arg82 kinase activity for PHO5 transcription and chromatin remodeling in budding yeast. The concluding passage suggests a role for IP4 and/or IP5, but does not identify Ins(1,4,5,6)P4 specifically; that part of the attributed claim is more specific than the paper supports. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIPMK has roles in nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.
“Initially identified in yeast and later recognized as essential for mammalian embryonic development, IPMK has transitioned from a niche interest to a focal point in studies of nutrient sensing, growth factor signaling, mRNA transport, and transcription regulation.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [19]
The paper’s Abstract identifies yeast ARG82/IPK2 as a nuclear inositol polyphosphate kinase and reports its role in phosphate-responsive transcription. It also states that Arg82 kinase activity is required for efficient mRNA export from the nucleus. Our copy does not establish roles in growth factor signaling or nutrient sensing broadly, nor does it address mammalian embryonic development. (LLM, conf=0.88)
Experimental — accuracy not yet measuredInsP4 and/or InsP5 generated by IPK2 are crucial for modulating SWI/SNF and INO80 complexes' ability to induce transcription of phosphate-responsive genes.
“Mutational analysis revealed that InsP4 and/or InsP5, generated by IPK2, are crucial for modulating SWI/SNF and INO80 complexes’ ability to induce transcription of phosphate-responsive genes [19].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [19]
The Abstract reports that ARG82/IPK2 mutants have impaired PHO5 transcription and reduced recruitment of SWI/SNF and INO80 to phosphate-responsive promoters. It concludes that IP4 and/or IP5 production may modulate these complexes’ ability to induce some phosphate-responsive genes, but presents that link as a suggestion rather than establishing that the molecules are crucial for phosphate-responsive genes generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDepletion of IPMK (IPK2/Arg82) hinders recruitment of SWI/SNF and INO80 chromatin remodeling complexes to promoters of phosphate-responsive genes PHO5 and PHO8.
“In their study, depletion of IPMK, also known as IPK2 or Arg82, hindered the recruitment of SWI/SNF and INO80 chromatin remodeling complexes to the promoters of phosphate-responsive genes such as PHO5 and PHO8 (Figure 3C).”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [19]
The passage on ChIP experiments (section labeled Abstract; page unavailable) reports that deleting ARG82 reduced Ino80 recruitment to PHO5 and PHO84, and Snf2 (SWI/SNF) recruitment to PHO84. The paper names PHO84, not PHO8, and says it could not detect substantial Snf2 recruitment to PHO5; it therefore does not support reduced recruitment of both complexes to both promoters named in the claim. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIPMK functions in mRNA export, chromatin remodeling, transcription, nutrient sensing, and growth factor signaling.
“Its diverse functions span a wide range of cellular processes, including mRNA export [17,18], chromatin remodeling [19,20], transcription [21,22], nutrient sensing [23], and growth factor signaling [15].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [19]
IPMK's role in regulating chromatin remodeling and transcription was first discovered by Steger et al. in yeast.
“The pivotal role of IPMK in regulating chromatin remodeling and transcription was first discovered by Steger et al. in yeast [19].”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [19]
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“Several further studies have supported the importance of Arg 82 kinase activity in transcriptional regulation and chromatin remodellin”
BackgroundModulation of ATP-Dependent Chromatin-Remodeling Complexes by Inositol Polyphosphates
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“Its diverse functions span a wide range of cellular processes, including mRNA export [17,18], chromatin remodeling [19,20], transcription [21,22], nutrient sensing [23], and growth factor signaling [15].”
Influential
- Authors
- Steger, D. J., Haswell, E. S., Miller, A. L., Wente, S. R., & O'Shea, E. K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Vanderbilt University Medical Center (US)
- Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143–0448, USA.
- Corresponding author
- Haswell, Elizabeth S.
- Venue
- Science
- Published
- 2003-01-03
- Volume
- 299
- Issue
- 5603
- Pages
- 114-116
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC1458531
- OpenAlex
- W2159070856
- Cited by
- 352
- References
- 25
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 11 · 2019: 8 · 2018: 3 · 2017: 14 · 2016: 11 · 2015: 12 · 2014: 12 · 2013: 16 · 2012: 21
- FWCI
- 14.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM-51219, GM51377, R01GM051377)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- chromatin remodeling, inositol polyphosphates, inositol polyphosphate kinase, PHO5 promoter, SWI/SNF complex, INO80 complex, transcriptional regulation, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphatases, Chromatin, DNA-Binding Proteins, Saccharomycetales, Fungal Proteins, Inositol Phosphates, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Point Mutation, Phosphotransferases (Alcohol Group Acceptor), Phosphate Transport Proteins, Proton-Phosphate Symporters, Saccharomyces cerevisiae Proteins
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