October 2009

GENETICS:

Unraveling the Biochemistry of Epigenetic Inheritance

Most people are aware that genetic information is passed down from generation to generation, and that this information is controlled by the DNA sequence of your cells. Many people are unaware that information can be passed down from generation to generation through another mechanism, known as epigenetic inheritance.

This occurs when the protein content of cells varies over a time scale longer than the time required for a cell to divide. The DNA sequence of the new cells may be identical, yet the cells still possess different observable features.

This method of inheritance has medical and other consequences. For example, last year a group of scientists found that starvation during the World War 2 "Dutch Hunger Winter" had life-long genetic consequences.

Consequently, many scientists would like to study epigenetics in detail, at the cellular level. A complication of interpreting the results of such experiments has been that, to date, the experiments have been performed in a large collection of freely-moving cells.

Therefore, only average changes among a large population of cells has been observed. Changes within a single cell lineage, which may be different from overall average behavior, have not been thoroughly investigated.

Amy Rowat, David Weitz (Harvard University), and coworkers have begun to fill in this gap in our knowledge. They have cheaply fabricated a device that enables individual cells and their specific progeny to be tracked and observed over time with a microscope.

Observing cell lineages.

The scientists' device consists of a series of long channels. Each channel possesses a large open end (large enough to let in a single cell) and a small open end (small enough to prevent the cell from leaving, but large enough to let salt water through the opening).

When a cell migrates from the large open end to the small open end of one of these channels, the flow of water through the channel is reduced. This restricted flow prevents other cells from migrating into that specific channel.

Thus, each channel originally possesses no more than one cell. Additionally, each channel is long enough to accommodate the progeny of that cell.

This keeps the progeny cells within the channel and prevents them from mixing with other cells in neighboring channels. Furthermore, the scientists are able to easily change the local environment of the cells, e.g., through changing the identity or other conditions of the salt water flowing through the cell chambers.

This enables one to study the effect of local environment on epigenetic inheritance (observable features of cells which are not dictated by DNA sequence). Data is obtained from multiple cell lineages, all kept separate from one another.

Time course of epigenetic inheritance.

The scientists utilized their device to track epigenetic changes in specific cell lines over time, as a function of salt water (local environment) concentration. Specifically, they were able to monitor changes in the expression of three different proteins in cell lineages over time.

They found that expression of the proteins pPho84 and Rps8b can vary over a time scale longer than cell division, while variation of expression of the protein Hsp12 doesn't take as long. Furthermore, protein Hsp12 expression levels increase among all cells in a lineage simultaneously, while that of Rps8b does not vary over time in this manner.

Future development.

These scientists' experiments were performed with yeast, which are easy to handle and grow quickly. However, there's no reason to believe that analogous experiments cannot be performed with bacterial and mammalian cells, which are of greater relevance to human health.

for more information:
Rowat, A. C., Bird, J. C., Agresti, J. J., Rando, O. J., & Weitz, D. A. (2009). Tracking lineages of single cells in lines using a microfluidic device Proceedings of the National Academy of Sciences, 106 (43), 18149-18154 DOI: 10.1073/pnas.0903163106