Related Experiment Video

Updated: Apr 6, 2026

Author Spotlight: Developing Acetyl-Click Assay for HAT1 Inhibitor Screening
05:44

Author Spotlight: Developing Acetyl-Click Assay for HAT1 Inhibitor Screening

Published on: January 26, 2024

1.5K

Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors

David C Montgomery1, Alexander W Sorum1, Laura Guasch1

  • 1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick MD, 21702, USA.

Chemistry & Biology
|July 21, 2015
PubMed

Insights

Fatty acyl-CoAs, like palmitoyl-CoA, regulate histone acetylation by inhibiting lysine acetyltransferase (KAT) enzymes. This discovery links cellular metabolism to epigenetic modifications in cancer.

Area of Science:

  • Biochemistry
  • Epigenetics
  • Cancer Metabolism

Background:

  • Chromatin modifications link cellular metabolism and gene expression.
  • Specific metabolic-epigenetic axes in cancer remain poorly understood.
  • Understanding these axes is crucial for developing cancer therapeutics.

Purpose of the Study:

  • To define the metabolic regulation of lysine acetyltransferase (KAT) enzymes.
  • To identify metabolites that modulate KAT activity.
  • To explore novel therapeutic strategies targeting metabolic-epigenetic signaling in cancer.

Main Methods:

  • Development of a novel chemoproteomic probe.
  • Identification of metabolite-enzyme interactions.
  • Assessment of fatty acyl-CoA effects on KAT activity and cellular histone acetylation.

Main Results:

  • A previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes was identified.
  • Palmitoyl-CoA was found to be a potent inhibitor of KAT activity.
  • Fatty acyl-CoA precursors were shown to reduce cellular histone acetylation levels.

Conclusions:

  • Fatty acyl-CoAs act as endogenous regulators of histone acetylation.
  • This study implicates fatty acyl-CoAs in epigenetic signaling.
  • Novel strategies for investigating and modulating epigenetic signaling through metabolism are suggested.

More Related Videos

Assays for Validating Histone Acetyltransferase Inhibitors09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

7.2K
Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

8.8K

Related Concept Videos

Histone Modification02:32

Histone 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...
17.3K
Histone Modification02:32

Histone Modification

5.0K
Covalently Linked Protein Regulators02:04

Covalently 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....
9.9K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.9K
Spreading of Chromatin Modifications02:25

Spreading 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...
10.0K
Phase II Reactions: Acetylation Reactions01:24

Phase II Reactions: Acetylation Reactions

Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
1.0K