Regulated Noise in the Epigenetic Landscape of Development and Disease


In this Perspective, we synthesize past and present observations in the field of epigenetics to propose a model in which the epigenome can modulate cellular plasticity in development and disease by regulating the effects of noise. In this model, the epigenome facilitates phase transitions in development and reprogramming and mediates canalization, or the ability to produce a consistent phenotypic outcome despite being challenged by variable conditions, during cell fate commitment. After grounding our argument in a discussion of stochastic noise and nongenetic heterogeneity, we explore the hypothesis that distinct chromatin domains, which are known to be dysregulated in disease and remodeled during development, might underlie cellular plasticity more generally. We then present a modern portrayal of Waddington's epigenetic landscape through a mathematical formalism. We speculate that this new framework might impact how we approach disease mechanisms. In particular, it may help to explain the observation that the variability of DNA methylation and gene expression are increased in cancer, thus contributing to tumor cell heterogeneity.

DOI: 10.1016/j.cell.2012.02.045

Extracted Key Phrases

2 Figures and Tables

Citations per Year

466 Citations

Semantic Scholar estimates that this publication has 466 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Pujadas2012RegulatedNI, title={Regulated Noise in the Epigenetic Landscape of Development and Disease}, author={E. Pujadas and Andrew P. Feinberg}, journal={Cell}, year={2012}, volume={148}, pages={1123-1131} }