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Metabolic regulation of chromatin modifications and gene expression
Open accessAbstract
Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways. In addition, several of the enzymes that can remove these marks use metabolites as part of their enzymatic reaction. These observations have led to the hypothesis that fluctuations in metabolite levels influence the deposition and removal of chromatin modifications. In this review, we consider the emerging evidence that cellular metabolic activity contributes to gene expression and cell fate decisions through metabolite-dependent effects on chromatin organization.
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“In particular, glutamine-derived α-KG has been implicated in regulating cellular histone and DNA methylation levels98.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [98]
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“In these reactions, α-KG is oxidized to succinate, and increasing levels of succinate can suppress the progression of α-KG-dependent histone or DNA demethylase reactions98.”
From Glutamine reliance in cell metabolism (2020) · cites this paper as [98]
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“By co-opting the production and localization of select TCA cycle metabolites, cells can modulate the activity of chromatin-modifying enzymes and exert control over gene expression and cell fate (158, 159, 160).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [159]
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Metadata
- Authors
- Schvartzman, J. M., Thompson, C. B., & Finley, L. W. S.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Finley, Lydia W.S.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2018-05-14
- Volume
- 217
- Issue
- 7
- Pages
- 2247-2259
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC6028552
- OpenAlex
- W2804524416
- Cited by
- 233
- References
- 124
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 26 · 2023: 32 · 2022: 22 · 2021: 33 · 2020: 36 · 2019: 34 · 2018: 5
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Hope Funds for Cancer Research
- Damon Runyon Cancer Research Foundation (DFS-23-17)
- Memorial Sloan Kettering Cancer Center (P30 CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromatin modification, gene expression regulation, cellular metabolism, histone modifications, DNA modification, transcription factors, cell fate determination, chromatin organization
- MeSH terms
- Chromatin, Gene Expression Regulation, Histones, Humans, Cell Lineage, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Metabolic Networks and Pathways
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