Scientists probing the genetic secrets of stem cells have discovered a number of genes and proteins that could partly account for their remarkable properties. Genetics is one part of the problem and epigenetics brings an extra dimension. In regards to the latter, Amanda Fisher and her colleagues at the MRC Clinical Sciences Centre have made an intriguing discovery.

They decided to compare the histone tail patterns found in ES cells to those of less flexible stem cells, like adult stem cells that make blood. Surprisingly, histones near a number of genes in ES cells had conflicting tags. They were simultaneously flagged for activity, but tagged with silencing marks. This seemingly confusing instruction to nearby genes is currently a hot research topic.

The double-tagged genes are involved in helping different kinds of cell to differentiate. So Fisher and her team hypothesised that active markers primed the genes to switch on at a certain stage in the differentiation process, while the silencing tags kept the gene on hold until time and place were right (see Azuara et al 2006). To confirm their hunch, they looked at cells that couldn’t make the silent marks. Sure enough, these cells did not differentiate properly, switching these genes on too early.

About the same time, a team headed by Bradley Bernstein of the Broad Institute and Harvard Medical School in Massachusetts had come to very similar conclusions. Bernstein and his team had studied the control regions of genes that code for transcription factors known to be important for the differentiation of different types of cells. They too discovered that such genes contained both activating and repressing histone marks. What’s more, ES cells contained many more of these bivalent marks than differentiated cells (see Bernstein et al 2006).