Magic 'switch' for mammals to sense chromosome number

The cells of female mammals have dosing issues because they have twice as many X chromosomes as the human body needs

But how does a cell know to turn off one chromosome at a given time -- but only when there are two?

A research team led by Lise Meitner's group leader Edda Schulz at the Max Planck Institute for Molecular Genetics (MPIMG) has found the answer to this decades-long puzzle in mouse stem cells and put their research together The results were published in the journal Molecular Cell

A new genetic circuit

Scientists in Berlin have discovered a genetic circuit that receives information about the stage of a cell's development and passes it on to the Xist gene

The newly discovered gene switch, called "Xert," is a member of a family of regulatory sequences called "enhancers

The DNA elements around existentialism process information from different sources, like a computer, Schulz said: "A cell has programs that can be started and stopped

Gain insight through disruption

"Our goal is to trace genetic circuits without knowing the schematic," said Rutger Gjaltema, a scientist in Schulz's lab and the paper's first author

In an initial screening experiment, the scientists identified 138 DNA segments on the X chromosome that appeared to be involved in some way in signal transduction around the genes present

"We found a lot of Xist regulators that we already knew about, which was a good sign because it confirmed our approach was working, of course, what's even more exciting is that a lot of completely unknowns came up in the analysis sequence

division of labor in space

To study the function of the new sequences, the scientists compared their activity in stem cells, developing cells, and cells with two or only one X chromosome

The first switch is located adjacent to the Xist and its activation sequence

The second switch isn't located near Xist, Schulz explained: "Like other developmental genes, the enhancer is relatively far from the target gene

"The two signaling pathways are interconnected," Schulz said

Models for other developmental genes

These new findings provide clues for further studies of X chromosome inactivation, Schulz said

Rutger AF Gjaltema, Till Schwämmle, Pauline Kautz, Michael Robson, Robert Schöpflin, Liat Ravid Lustig, Lennart Brandenburg, Ilona Dunkel, Carolina Vechiatto, Evgenia Ntini, Verena Mutzel, Vera Schmiedel, Annalisa Marsico, Stefan Mundlos, Edda G .