Related Experiment Video
Updated: Apr 20, 2026
08:12
Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
Published on: May 5, 2022
4.7K
Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes
Zachary Castonguay1, Christopher Auger1, Sean C Thomas1
1Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario P3E 2C6, Canada.
Biochemical and Biophysical Research Communications
|December 3, 2014
Summary
A newly identified nuclear lactate dehydrogenase (nLDH) isoform controls histone deacetylation by regulating nicotinamide adenine dinucleotide (NAD(+)) availability. This metabolic enzyme links cellular metabolism to epigenetic modifications under oxidative stress.
Area of Science:
- Cell Biology
- Epigenetics
- Metabolic Biochemistry
Background:
- The nucleus contains metabolic enzymes influencing genetic events.
- Nuclear lactate dehydrogenase (nLDH) and its role in epigenetic regulation are under investigation.
Purpose of the Study:
- To describe a nuclear isoform of lactate dehydrogenase (nLDH).
- To investigate the mechanism by which nLDH controls histone deacetylation via nicotinamide adenine dinucleotide (NAD(+)) availability.
- To explore the link between nLDH, oxidative stress, and epigenetic modifications.
Main Methods:
- Characterization of nuclear lactate dehydrogenase (nLDH) expression.
- Measurement of nicotinamide adenine dinucleotide (NAD(+)) levels.
- Assessment of histone deacetylation.
- Co-immunoprecipitation assays to determine enzyme interactions.
Main Results:
- nLDH expression increased with hydrogen peroxide (H2O2) exposure.
- nLDH generated NAD(+) under oxidative stress, enhancing histone deacetylation.
- No significant change in sirtuin-1 (SIRT1) levels was observed.
- nLDH and SIRT1 were found to co-immunoprecipitate, indicating an association.
Conclusions:
- nLDH plays a critical role in regulating epigenetic modifications by controlling nuclear NAD(+) levels.
- This highlights a direct link between cellular metabolism and the processing of genetic information.
- nLDH represents a novel molecular link between metabolic state and epigenetic control.
More Related Videos
Related Concept Videos
02:32Histone Modification
18.0K
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...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
18.0K
02:32Histone Modification
5.1K
5.1K
02:25Spreading of Chromatin Modifications
10.1K
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...
Writers
The writer...
10.1K
03:17Inheritance of Chromatin Structures
8.0K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
8.0K
01:32Chromatin Modification in iPS Cells
2.3K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.3K
01:58Cell Specific Gene Expression
17.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
17.5K