ArticleMolecular cell2013
Histone acetylation regulates intracellular pH.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.
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Who cites it
155 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- The symbiotic axis between the acidic tumor microenvironment and cancer stem cells: a driver of malignancy and therapeutic resistance.Frontiers in oncology · 2026Review
- pH sensing and inflammation: linking acidic microenvironments to immune reprogramming.Frontiers in immunology · 2026Review
- Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy.Theranostics · 2026Review
- IVF and Thermal Manipulation at the First Cleavage Stage Alter Offspring Circadian Phenotype, Sleep, and Brain Epigenetics.International journal of molecular sciences · 2025Article
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- Epigenetics of Endometrial Cancer: The Role of Chromatin Modifications and Medicolegal Implications.International journal of molecular sciences · 2025Review
- Valproic Acid Promotes the Differentiation of Satellite Glial Cells into Neurons via the pH-Dependent Pathway.Biomolecules · 2025Article
- Coordinated histone methylation loss and MYC activation promote translational capacity under amino acid restriction.Cancer & metabolism · 2025Article
- Control of Inflammatory Response by Tissue Microenvironment.bioRxiv : the preprint server for biology · 2025Article
- Decoding a novel non-enzymatic protein acetylation mechanism in sperm that is essential for fertilizing potential.Biological research · 2025Article
- Autophagy mediated immune response regulation and drug resistance in cancer.Molecular biology reports · 2025Review
- A role for pH dynamics regulating transcription factor DNA-binding selectivity.Nucleic acids research · 2025Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
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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