Related Experiment Video

Updated: Jul 9, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Competitive inhibition of histone deacetylase activity by trichostatin A and butyrate

Anoushe Sekhavat1, Jian-Min Sun, James R Davie

  • 1MB Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba, Canada.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|December 7, 2007
PubMed

Insights

Histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and butyrate competitively inhibit HDAC activity. TSA treatment does not disrupt HDAC1/HDAC2 interactions with Sin3A or Sp1 in breast cancer cells.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Histone deacetylases (HDACs) are crucial for gene expression and chromatin remodeling.
  • Aberrant HDAC activity is implicated in various cancers, making HDAC inhibitors potential anti-tumor agents.
  • Conflicting data exists regarding the inhibition mechanism of HDAC inhibitors like trichostatin A (TSA).

Purpose of the Study:

  • To clarify the inhibitory mechanism of HDAC inhibitors TSA and butyrate.
  • To investigate the effect of TSA on protein-protein interactions involving HDAC1 and HDAC2.

Main Methods:

  • Enzyme kinetics assays to determine inhibition type.
  • Co-immunoprecipitation to assess protein complex stability.

Main Results:

  • TSA and butyrate were confirmed to be competitive inhibitors of HDAC activity.
  • TSA did not affect the association of HDAC1 and HDAC2 with Sin3A in MCF-7 cells.
  • TSA also did not interfere with the interaction between HDAC2 and transcription factor Sp1.

Conclusions:

  • The study resolves conflicting data, establishing TSA and butyrate as competitive HDAC inhibitors.
  • HDAC inhibitor TSA maintains the stability of repressor complexes like Sin3 and does not disrupt interactions with transcription factors.
  • These findings support the therapeutic potential of TSA in cancer treatment by clarifying its mechanism of action.

More Related Videos

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS09:20

Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS

Published on: August 10, 2017

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue08:12

Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue

Published on: May 5, 2022

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 deacetylase,...
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 deacetylase,...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
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 is an enzyme that can...
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...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...