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Theoretical analysis of epigenetic cell memory by nucleosome modification.

Ian B Dodd1, Mille A Micheelsen, Kim Sneppen

  • 1Center for Models of Life, Niels Bohr Institute, Blegdamsvej 17, DK-2100, Copenhagen Ø, Denmark.

Cell
|May 22, 2007
PubMed
Summary

Epigenetic gene expression can be bistable due to nucleosome modification. A model shows this bistability requires cooperative modification and non-local effects, not just simple spreading.

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Area of Science:

  • Epigenetics and molecular biology
  • Computational biology and systems biology

Background:

  • Chromosomal regions exhibit stable, heritable alternative states of gene expression without DNA sequence alteration.
  • Epigenetic control is linked to histone covalent modifications, with positive feedback mechanisms proposed for state stability.

Purpose of the Study:

  • To develop a simplified stochastic model of dynamic nucleosome modification.
  • To investigate the mechanisms underlying bistable gene expression in epigenetic regulation, using yeast as a model.

Main Methods:

  • Developed a simplified stochastic model for nucleosome modification dynamics.
  • Simulated the model using parameters relevant to the silent mating-type region of *Schizosaccharomyces pombe*.

Main Results:

  • The model demonstrated strong bistability resistant to noise from modification gain/loss and DNA replication.
  • Robust bistability necessitated cooperative modification involving multiple nucleosomes.
  • Observed non-local stimulation of modification beyond immediate neighbors, challenging simple spreading models.

Conclusions:

  • A simplified stochastic model can recapitulate robust epigenetic bistability.
  • Cooperative and non-local nucleosome modification mechanisms are crucial for stable epigenetic states.
  • Findings provide insights into the molecular basis of heritable gene expression patterns.