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Related Concept Videos

Histone Variants at the Centromere02:30

Histone Variants at the Centromere

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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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.
X-chromosome...
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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.
Acetylation
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Loss of Tumor Suppressor Gene Functions01:12

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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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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Adaptive Mechanisms in Cancer Cells

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy
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Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy

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Histone mutations in cancer.

Kimberly N Espinoza Pereira1, Jixiu Shan1, Jonathan D Licht1

  • 1UF Health Cancer Center, University of Florida, Gainesville, FL 32610, U.S.A.

Biochemical Society Transactions
|September 18, 2023
PubMed
Summary
This summary is machine-generated.

Histone mutations, or oncohistones, disrupt normal chromatin structure and drive cancer development across many tumor types. These mutations impact gene regulation, leading to cancer phenotypes.

Keywords:
cancerchromatinhistonespoint mutations

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Genes encoding histone proteins are frequently mutated in tumors.
  • These mutations can affect nucleosome stability, histone modifications, and chromatin dynamics.
  • The widespread occurrence of histone mutations suggests chromatin integrity is crucial for preventing cancer.

Purpose of the Study:

  • To survey histone mutations in cancer.
  • To review the function and role of histone mutations in tumorigenesis.

Main Methods:

  • Literature review of studies on histone mutations in cancer.
  • Analysis of the functional impact of specific oncohistone mutations.

Main Results:

  • Oncohistone mutations disrupt chromatin structure and gene regulation.
  • Aberrant gene expression driven by oncohistones contributes to cancer phenotypes.
  • Examples include H3 K27M in pediatric brain cancers and H2B E76K in solid tumors.

Conclusions:

  • Oncohistones, though potentially a small fraction of total histones, can have global effects on chromatin.
  • Histone mutations represent a significant mechanism in cancer development.
  • Understanding oncohistones offers insights into cancer biology and potential therapeutic targets.