Monday, April 04, 2011

Newly discovered epigenetic tag offers insight into embryonic stem cell regulation

Source: Biotechnology and Biological Sciences Research Council
Date: 4 April 2011

Summary:

Scientists from the Babraham Institute have gained a new understanding of how molecular signals and switches control how an embryo develops into an adult. The new research, published today (3 April) in the journal Nature, details how a newly discovered form of epigenetic regulation controls the development of embryonic stem (ES) cells.

The research, funded by BBSRC, MRC, the University of Cambridge and EPIGENOME, has important implications for regenerative medicine as it could offer new methods for controlling how ES cells differentiate in every cell in the human body and, potentially, to the growing field of induced pluripotent stem (iPS) cells where adult stem cell are 'reprogrammed'.

Embryonic stem (ES) cells are pluripotent cells present in the early embryo, which have the capacity to differentiate into all the specialised cells that make up the adult body. As an embryo develops, the cells respond to signals and differentiate to acquire a particular fate, for example a skin cell. Cell fate is governed not only by the genome, but also by chemical changes to DNA that alter the DNA structure but not its sequence. These 'epigenetic' tags are one of the ways that genes get switched on or off in different places at different times, enabling different tissues and organs to arise from a single fertilised egg and also helps to explain how our genes can be influenced by the environment.

The new research reveals that a new type of epigenetic modification, 5-hydroxymethylcytosine (5hmC), plays a critical role mediating the external signals that instruct a cell how to develop; this tiny chemical tag (5hmC) is attached to or removed from the genetic sequence depending on the message received, switching genes on or off. The researchers managed to identify the location of this tag throughout the genome, using high throughput sequencing methods. They observed for so called pluripotency-related genes that, as 5hmC decreases, another previously known epigenetic modification, 5-methylcytosine (5mC) increases - this shift has consequences in determining how genes function and hence a cell's developmental fate.