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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

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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.
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Epigenetic Regulation01:46

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Mismatch Repair01:20

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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Overview
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Spreading of Chromatin Modifications02:25

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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.
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DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge.

Omar Castillo-Aguilera1, Patrick Depreux2, Ludovic Halby3

  • 1Univ. Lille, ICPAL, EA 7365-GRITA-Groupe de Recherche sur les formes Injectables et les Technologies Associées, 3 rue du Pr. Laguesse, F-59000 Lille, France. omar.castilloaguilera@univ-lille2.fr.

Biomolecules
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Epigenetic modifications like DNA and histone methylation control gene expression. Altered methylation patterns in cancer suggest targeting these modifications with inhibitors is a promising therapeutic strategy.

Keywords:
DNA methylationDNMT inhibitorsDNMT/HMT crosstalkHMT inhibitorshistone methylation

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Biology

Background:

  • Chromatin exists in decondensed (euchromatin) and condensed (heterochromatin) states, regulating gene transcription and repression.
  • Epigenetic modulators, including DNA and histone methyltransferases, control these chromatin states through methylation.
  • Aberrant DNA and histone methylation patterns are hallmarks of cancer, highlighting their therapeutic relevance.

Purpose of the Study:

  • To present a comprehensive classification of DNA methyltransferase inhibitors based on their mechanisms of action.
  • To identify and discuss histone methyltransferase inhibitors that share a common mode of action.
  • To underscore the therapeutic potential of targeting epigenetic modifications in cancer treatment.

Main Methods:

  • Systematic review and classification of known DNA methyltransferase inhibitors.
  • Identification and analysis of histone methyltransferase inhibitors with shared mechanisms.
  • Literature-based compilation and categorization of epigenetic modulators.

Main Results:

  • A detailed classification of DNA methyltransferase inhibitors is provided, categorized by their specific mechanisms.
  • A selection of histone methyltransferase inhibitors with a common mode of action is presented.
  • The study highlights the intricate crosstalk between DNA and histone methylation in gene regulation.

Conclusions:

  • Targeting DNA and histone methylation represents a viable therapeutic strategy for cancers with altered epigenetic landscapes.
  • Understanding the mechanisms of epigenetic modulators is crucial for developing effective cancer therapies.
  • The presented classification aids in the strategic development of novel epigenetic drugs.