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Related Concept Videos

Histone Modification02:32

Histone Modification

16.9K
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...
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Histone Modification02:32

Histone Modification

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Heterochromatin02:38

Heterochromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
18.9K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

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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...
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Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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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...
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Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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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...
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Assays for Validating Histone Acetyltransferase Inhibitors
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Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors.

Linda Schäker-Hübner1, Finn K Hansen1

  • 1Pharmaceutical Institute, University of Bonn, An der Immenburg 4, Bonn 53121, Germany.

ACS Pharmacology & Translational Science
|March 19, 2026
PubMed
Summary

Developing selective histone deacetylase inhibitors (HDACi) is complex. This review reevaluates HDACi tool compounds, discussing limitations for investigating HDAC isoform functions.

Keywords:
HDAC assayHDAC inhibitorchemical probehistone deacetylase (HDAC)tool compound

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • Histone deacetylase inhibitors (HDACi) are crucial tools in biological research.
  • Oversimplified assays have led to overinterpretation of HDACi selectivity and function.
  • Recent data on HDAC structure and kinetics necessitate reevaluation of existing studies.

Purpose of the Study:

  • To review and critically assess chemical probes for studying histone deacetylase (HDAC) isoforms.
  • To provide guidance on selecting appropriate tool compounds for biological and pharmacological investigations.
  • To highlight the limitations of current HDAC inhibitors based on updated scientific insights.

Main Methods:

  • Literature review of biochemical assays and HDAC inhibitor studies.
  • Analysis of recent data on HDAC isoform structure, binding kinetics, and substrate specificity.
  • Critical evaluation of commonly used HDAC inhibitor tool compounds.

Main Results:

  • Many previously used HDACi lack true isoform selectivity.
  • Oversimplified biochemical assays often yield misleading results regarding HDAC inhibition.
  • Current understanding of HDAC biology requires a more nuanced approach to inhibitor selection.

Conclusions:

  • Reevaluation of studies using supposedly isoform-selective HDACi is essential.
  • Careful selection of tool compounds is critical for accurate investigation of HDAC isoform functions.
  • Further development of selective HDAC inhibitors and robust assay methods is needed.