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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,...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

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 DNA...

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Extraction of Histones from Clinical Specimens for Epigenetic Profiling by Mass Spectrometry
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Oncoepigenomics: making histone lysine methylation count.

Daniel Decarlo1, M Kyle Hadden

  • 1Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd., Unit 3092, Storrs, CT 06269-3092, USA.

European Journal of Medicinal Chemistry
|September 15, 2012
PubMed
Summary

Histone lysine methylation impacts diseases like cancer and diabetes. This review covers progress in targeting histone methyltransferases (KMTs) and demethylases (KDMs) for therapeutic development.

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Area of Science:

  • Epigenetics
  • Molecular Biology
  • Oncology

Background:

  • Histone lysine methylation is increasingly linked to diseases including schizophrenia, diabetes, and cancers.
  • Epigenetic alterations, particularly histone modifications, are critical drivers of disease pathology.
  • Targeting enzymes involved in histone methylation offers a promising therapeutic strategy.

Purpose of the Study:

  • To provide a comprehensive review of current advancements in targeting histone lysine methyltransferases (KMTs) and demethylases (KDMs).
  • To highlight the role of KMTs and KDMs in tumor growth and progression.
  • To discuss the development of small molecules designed to modulate these epigenetic enzymes.

Main Methods:

  • Literature review of recent studies on histone lysine methylation.
  • Analysis of the role of KMTs and KDMs in various disease models, with a focus on cancer.
  • Survey of small molecule inhibitors and activators targeting KMTs and KDMs.

Main Results:

  • KMTs and KDMs are crucial regulators of gene expression with significant roles in disease pathogenesis.
  • Dysregulation of histone methylation is a hallmark of numerous human cancers, influencing tumor initiation and metastasis.
  • Several small molecules targeting KMTs and KDMs are in preclinical and clinical development for cancer therapy.

Conclusions:

  • Targeting KMTs and KDMs represents a significant frontier in epigenetic therapy for diseases like cancer.
  • Further research into the precise roles and modulation of these enzymes will accelerate the development of novel therapeutics.
  • Small molecule modulators offer a viable approach to correct aberrant epigenetic states in disease.