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Heritable stochastic switching revealed by single-cell genealogy
Benjamin B Kaufmann1, Qiong Yang, Jerome T Mettetal
1Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Plos Biology
|September 7, 2007
Summary
Cellular factors inherited during division synchronize epigenetic state switching in yeast families. This non-genetic inheritance influences gene expression for several generations before random processes dominate.
Area of Science:
- Cell Biology
- Epigenetics
- Yeast Genetics
Background:
- Cell division involves partitioning cellular factors like proteins and RNAs.
- Nongenetic inheritance's quantitative impact on gene expression changes remains poorly understood.
- Epigenetic states are semi-stable and can be inherited.
Purpose of the Study:
- To quantitatively measure the effect of nongenetic inheritance on epigenetic state switching.
- To understand how inherited cellular factors influence synchronized cell behavior.
- To investigate the role of stochastic processes in epigenetic state evolution.
Main Methods:
- Tracking families of Saccharomyces cerevisiae through cell division.
- Analyzing epigenetic state switching patterns over multiple generations.
- Comparing observed switching times to a Poisson process model.
- Developing a stochastic model involving fluctuating regulatory proteins.
Main Results:
- Yeast cell families exhibited synchronized epigenetic state switching long after division.
- Individual cells showed exponentially distributed switching times.
- Inherited factors initially dictated the time evolution of epigenetic states.
- Stochastic processes took several generations to decorrelate related cells.
- A model with a single, burst-synthesized regulatory protein explained the observed dynamics.
Conclusions:
- Nongenetic inheritance plays a crucial role in coordinating epigenetic states in early cell generations.
- Stochasticity in gene expression, influenced by factors like bursty protein synthesis, underlies epigenetic state dynamics.
- Understanding these mechanisms is key to comprehending cellular memory and phenotypic variation.
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