Related Experiment Video
Updated: May 16, 2026
09:43
Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
Published on: November 30, 2018
Histone acetylation regulates intracellular pH
Matthew A McBrian1, Iman Saramipoor Behbahan, Roberto Ferrari
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Molecular Cell
|December 4, 2012
Summary
Histone acetylation regulates intracellular pH (pH(i)). Decreasing pH causes histone deacetylation and acetate export, while rising pH increases histone acetylation, impacting cell proliferation and HDAC inhibitor therapies.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Global histone acetylation levels differ between normal and cancer cells.
- The precise regulatory role of histone acetylation in cellular homeostasis remains largely undefined.
Purpose of the Study:
- To elucidate the function of histone acetylation in controlling intracellular pH (pH(i)).
- To investigate the relationship between pH(i) and histone acetylation dynamics.
Main Methods:
- Monitoring global histone acetylation and deacetylation.
- Utilizing histone deacetylase (HDAC) and monocarboxylate transporter (MCT) inhibitors.
- Assessing intracellular pH changes under varying conditions.
Main Results:
- Decreased pH(i) triggers global histone deacetylation, with acetate co-exported with protons via MCTs.
- Increased pH(i) leads to global histone hyperacetylation, observed during cell proliferation.
- Inhibition of HDACs or MCTs impairs acetate export, lowering pH(i), especially in acidic conditions.
Conclusions:
- Chromatin acetylation acts as a rheostat to modulate intracellular pH.
- Understanding this mechanism is crucial for the therapeutic application of HDAC inhibitors.
Related Concept Videos
01:28pH Regulation in Cells
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:02Phosphorylation
The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...