Gene Switches Hold Clues to "Family Tree"
If you wanted to draw your family tree, you could start by searching for people who share your gene switches.
Cells don’t have surnames, but scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have found that genetic switches called enhancers, and the molecules activating those switches transcription factors can be used as clues to a cell’s developmental history.
The study, published in Cell, also unveils a new model for how enhancers function.
Guillaume Junion and Mikhail Spivakov, collaborated to look at fruit fly embryos' heart muscle cells, finding active enhancers aren’t the only ones that have groups of transcription factors attached.
Surprisingly, enhancers that should be active only in the neighbouring gut muscle are also occupied by transcription factors in heart cells.
“Although it may seem counter-intuitive to leave unnecessary genetic switches available for activation and then have to actively suppress them, the findings make sense in developmental terms,” says Furlong.
Both heart and gut muscle cells develop from the same pool of precursor cells. Enhancers for both groups seem to be made available to transcription factors in the precursor cells, before they ‘grow up’ to be either heart or muscle cells.
If this is the case, scientists could work out the relationships between cells by looking at what occupied enhancers they share.
Intriguingly, heart muscle cells don’t actually have the transcription factors that bind to gut enhancers in gut muscle cells. Instead, the gut enhancers in heart cells were occupied by transcription factors produced only by the heart.
Furlong and colleagues found that transcription factors are able to attach themselves to enhancers in groups, others bind directly to the enhancer’s DNA and some bind to enhancer-bound transcription factors.
This means that the genetic sequence of these enhancers can vary greatly, even though they function as a united group a strategy that differs from the two ways in which enhancers were already known to function.
This flexibility in the enhancer’s genetic sequence means that it can mutate without disastrous effects, adding to the fruit fly's evolutionary flexibility.
The EMBL scientists are now investigating how far that flexibility goes.
They are looking at variation in another species of fruit fly, Drosophila virilis, which is genetically as different from the commonly-used Drosophila melanogaster as humans are from chickens.
Junion, G., Spivakov, M., Girardot, C., Braun, M., Gustafson, E.H., Birney, E. & Furlong, E.E.M. A transcription factor collective defines cardiac cell fate and reflects the developmental history of this cell lineage. Cell, 3 February 2012. DOI:10.1016/j.cell.2012.01.030.
Original article: http://www.embl.de/aboutus/communication_outreach/