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Histone Acetylation Regulates Intracellular pH
Open accessAbstract
Differences in global levels of histone acetylation occur in normal and cancer cells, although the reason why cells regulate these levels has been unclear. Here we demonstrate a role for histone acetylation in regulating intracellular pH (pH(i)). As pH(i) decreases, histones are globally deacetylated by histone deacetylases (HDACs), and the released acetate anions are coexported with protons out of the cell by monocarboxylate transporters (MCTs), preventing further reductions in pH(i). Conversely, global histone acetylation increases as pH(i) rises, such as when resting cells are induced to proliferate. Inhibition of HDACs or MCTs decreases acetate export and lowers pH(i), particularly compromising pH(i) maintenance in acidic environments. Global deacetylation at low pH is reflected at a genomic level by decreased abundance and extensive redistribution of acetylation throughout the genome. Thus, acetylation of chromatin functions as a rheostat to regulate pH(i) with important implications for mechanism of action and therapeutic use of HDAC inhibitors.
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“Cells are capable of buffering against extracellular reductions in pH to maintain alkaline pH of the cytoplasm (Johnson et al., 1976; L’allemain et al., 1984; Lindström and Sehlin, 1984; Pouyssegur et al., 1985; McBrian et al., 2013).”
From Toward Best Practices for Controlling Mammalian Cell Culture Environments (2022) · cites this paper as McBrian et al., 2013
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Metadata
- Authors
- McBrian, M. A., Behbahan, I. S., Ferrari, R., Su, T., Huang, T.-W., Li, K., Hong, C. S., Christofk, H. R., Vogelauer, M., Seligson, D. B., & Kurdistani, S. K.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Kurdistani, Siavash K.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 49
- Issue
- 2
- Pages
- 310-321
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3893119
- OpenAlex
- W1984600164
- Cited by
- 272
- References
- 53
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 29 · 2023: 13 · 2022: 20 · 2021: 17 · 2020: 29 · 2019: 22 · 2018: 24 · 2017: 15 · 2016: 32 · 2015: 13 · 2014: 18 · 2013: 9
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- American Cancer Society
- California Institute for Regenerative Medicine
- California Institute of Regenerative Medicine
- National Institutes of Health (1dp2od006516-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- 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
- Keywords
- histone acetylation, intracellular pH, histone deacetylase, monocarboxylate transporters, chromatin acetylation, pH homeostasis, histone deacetylase inhibitors, cancer cells, cell proliferation
- MeSH terms
- Acetates, Acetylation, Chromatin, Gene Expression Regulation, Glucose, Glutamine, HeLa Cells, Histone Deacetylases, Histones, Humans, Hydrogen-Ion Concentration, Hydroxamic Acids, Intracellular Fluid, Niacinamide, Protein Processing, Post-Translational, Sequence Analysis, RNA, Pyruvic Acid, Monocarboxylic Acid Transporters, Carbohydrate Metabolism, Histone Deacetylase Inhibitors, Transcriptome
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