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Related Concept Videos

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...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

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...
Chromatin Immunoprecipitation- ChIP02:36

Chromatin Immunoprecipitation- ChIP

Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
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,...
Heterochromatin02:38

Heterochromatin

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 9th...

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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Small-molecule chromatin-modifying agents: therapeutic applications.

Antonello Mai1

  • 1Pasteur Institute-Cenci Bolognetti Foundation, Drug Chemistry and Technologies Department, University of Rome Sapienza, Piazzale Aldo Moro 5, Rome, Italy. antonello.mai@uniroma1.it

Epigenomics
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PubMed
Summary

Histone deacetylase inhibitors (HDACi) show promise beyond cancer treatment. These compounds are effective in treating neurodegenerative diseases like Huntington's and Parkinson's, and have potential in antimalarial and antifungal therapies.

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Sequential Salt Extractions for the Analysis of Bulk Chromatin Binding Properties of Chromatin Modifying Complexes
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Published on: September 20, 2018

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)
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Published on: October 2, 2017

Area of Science:

  • Pharmacology
  • Oncology
  • Neuroscience

Background:

  • Suberoylanilide hydroxamic acid (vorinostat) is the first histone deacetylase inhibitor (HDACi) approved for cutaneous T-cell lymphoma.
  • Various HDACi classes, including short-chain fatty acids, hydroxamates, cyclic peptides, and benzamides, have been explored in clinical trials for diverse cancers.
  • HDACi also exhibit potential in antimalarial, antifungal, and HIV-1 reactivation therapies.

Purpose of the Study:

  • To review the therapeutic applications of HDAC inhibitors beyond oncology.
  • To highlight the efficacy of HDAC inhibitors in neurodegenerative diseases and infectious diseases.
  • To explore the potential of novel HDAC inhibitor classes, such as bis-anilides and sirtuin modulators.

Main Methods:

  • Literature review of clinical trials and preclinical studies involving HDAC inhibitors.
  • Analysis of data on HDAC inhibitor efficacy in various disease models.
  • Examination of the mechanisms of action for different HDAC inhibitor classes.

Main Results:

  • HDAC inhibitors have demonstrated efficacy in treating neurodegenerative conditions like Huntington's disease, Parkinson's disease, and Friedreich's ataxia.
  • Specific compounds, including bis-anilides and sirtuin inhibitors, show significant therapeutic potential.
  • SIRT2 inhibitors like AGK-2 offer neuroprotection in Parkinson's disease models, while sirtuin activators are beneficial for Alzheimer's disease.

Conclusions:

  • HDAC inhibitors represent a versatile class of drugs with broad therapeutic applications.
  • Their utility extends to oncology, neurodegenerative disorders, and infectious diseases.
  • Further research into novel HDAC inhibitors and their mechanisms of action is warranted for diverse therapeutic strategies.