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Related Concept Videos

Histone Modification02:32

Histone Modification

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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.
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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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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...
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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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Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
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Berberine acts as a putative epigenetic modulator by affecting the histone code.

Zhixiang Wang1, Yuan Liu2, Yong Xue3

  • 1Department of Hematology, Nanfang Hospital of Southern Medical University, Guangzhou, China.

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|June 18, 2016
PubMed
Summary

Berberine, a plant alkaloid, may affect gene expression by modulating epigenetic regulators. This study reveals berberine influences histone acetylation and methylation, impacting cell behavior and potential therapeutic applications.

Keywords:
BerberineEpigeneticHematological malignancyHistoneMethylation

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Epigenetics

Background:

  • Berberine, a plant alkaloid, has diverse bioactivities, but its precise mechanism is unclear.
  • Epigenetic modifications play crucial roles in regulating gene expression and cellular functions.

Purpose of the Study:

  • To investigate the potential epigenetic modulatory effects of berberine.
  • To identify berberine's molecular targets and affected pathways in epigenetic regulation.

Main Methods:

  • Reverse-docking analysis to predict berberine's targets.
  • PCR array analysis of epigenetic chromatin modification enzymes.
  • Real-time PCR and western blotting to validate gene and protein expression changes.

Main Results:

  • Berberine showed similarity to known epigenetic modulators, with lysine-N-methyltransferase identified as a putative target.
  • Berberine treatment significantly altered the expression of histone acetyltransferases, deacetylases, demethylases, and methyltransferases.
  • Downstream effects included changes in histone cluster gene expression and decreased levels of H3K4me3, H3K27me3, and H3K36me3 proteins.
  • These effects were confirmed in acute myelocytic leukemia (AML) cell lines.

Conclusions:

  • Berberine modulates the expression of key epigenetic regulators.
  • These modulations suggest berberine's potential to influence downstream pathways through epigenetic mechanisms.
  • Understanding these epigenetic effects could explain berberine's varied bioactivities and inform therapeutic strategies.