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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 profiling reveals a developmental decrease in promoter accessibility during cortical maturation in vivo.

Ishwariya Venkatesh1, Matthew T Simpson1, Denise M Coley1

  • 1Department of Biomedical Sciences, Marquette University, 53201.

Neuroepigenetics
|December 20, 2016
PubMed
Summary
This summary is machine-generated.

Axon regeneration in the adult central nervous system (CNS) is hindered by reduced expression of regeneration-associated genes (RAGs). Epigenetic changes restrict RAG access, limiting intrinsic axon growth potential in mature CNS neurons.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Epigenetics

Background:

  • Axon regeneration in the adult central nervous system (CNS) is significantly limited.
  • This limitation is partly due to a developmental decrease in the expression of regeneration-associated genes (RAGs) in injured neurons.
  • Adult CNS neurons may lack necessary pro-regenerative transcription factors or have restricted chromatin structures hindering RAG access.

Purpose of the Study:

  • To investigate the epigenetic mechanisms underlying the decline in RAG expression during CNS maturation.
  • To explore the potential of manipulating epigenetic factors and transcription factors to promote axon regeneration in adult CNS neurons.

Main Methods:

  • Performed epigenetic profiling around the promoter regions of key RAGs during cortical maturation.
  • Cultured postnatal cortical neurons to assess neurite outgrowth.
  • Tested the efficacy of various pro-regenerative interventions, including AP1 factor overexpression, histone acetyltransferase overexpression, and histone deacetylase inhibitors.

Main Results:

  • Epigenetic profiling revealed progressive chromatin structure restriction around RAG promoters during cortical maturation.
  • Cultured postnatal cortical neurons showed insensitivity to common pro-regenerative treatments.
  • This insensitivity suggests differences in cellular models and highlights intrinsic constraints on axon growth.

Conclusions:

  • Progressive chromatin closure during CNS maturation presents an intrinsic barrier to axon regeneration.
  • Standard pro-regenerative interventions are ineffective in cultured postnatal cortical neurons, indicating model-specific limitations.
  • Understanding these epigenetic constraints is crucial for developing effective strategies for CNS repair.