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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.
Acetylation
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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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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 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 mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Chromatin fiber allostery and the epigenetic code.

Annick Lesne1, Nicolas Foray, Guy Cathala

  • 1Laboratoire de Physique Théorique de la Matière Condensée, CNRS UMR 7600, UPMC Université Paris 06, Sorbonne Universités, F-75005, Paris, France. Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, Université de Montpellier, F-34293, Montpellier, France. CNRS GDR 3536, UPMC Université Paris 06, F-75005, Paris, France.

Journal of Physics. Condensed Matter : an Institute of Physics Journal
|January 8, 2015
PubMed
Summary

Histone modifications induce chromatin fiber allosteric transitions, regulating gene transcription. This epigenetic code, based on allosteric control, links histone modifications to transcriptional activity context-dependently.

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Structural Biology

Background:

  • Allostery, initially described for proteins, has been extended to DNA, where local structural changes influence remote DNA-binding events.
  • Histone-tail covalent modifications are known regulators of chromatin structure and gene expression.

Purpose of the Study:

  • To propose and articulate a model for chromatin fiber allosteric transitions.
  • To explain how histone modifications at the chromatin fiber level can regulate DNA-binding events and transcriptional regulation.
  • To provide a physical and mechanistic explanation for the correlation between histone modifications and transcriptional activity.

Main Methods:

  • Integrated scenario articulation of allosteric mechanisms across different scales.
  • Analysis of chromatin fiber mechanical constraints and DNA accessibility.
  • Case study using the mouse Igf2-H19 gene locus and its parental imprinting.

Main Results:

  • Histone-tail acetylation induces allosteric transitions in the condensed chromatin fiber.
  • These transitions alter DNA mechanical constraints, potentially controlling DNA-binding of transcription factors and other allosteric mechanisms.
  • Epigenetic constraints define distinct chromatin conformations favoring specific regulatory complex assembly.

Conclusions:

  • Chromatin fiber allosteric transitions, driven by histone modifications, are proposed as a key mechanism in transcriptional regulation.
  • This physical view offers a mechanistic explanation for the link between histone modifications and gene activity.
  • The evolutionary basis of allosteric control supports the concept of an 'epigenetic code' where histone modifications encode regulatory information in a context-dependent manner.