( Mandel created the acronym to describe ...)Gene keeps neural cells on correct developmental path

Since then, they and others have found that REST locks down neuronal genes in other cells by grabbing onto the DNA and cementing in other molecules, an arrangement that stays intact as non-neuronal cells differentiate into liver, muscle, and other tissues.

The new study reports that REST uses a different temporary off mechanism to direct neuronal development. "This study shows that there is more than one way to keep a REST-regulated gene repressed," said Michael G. Rosenfeld, an HHMI investigator at University of California, San Diego, who co-authored an accompanying commentary in Cell with Victoria Lunyak, a research associate in his lab.

In contrast to the tight packaging of neural genes in other cells, REST keeps the chromatin in embryonic stem and precursor neurons open and poised for gene activity.

"REST keeps the brake on lightly until a trigger tells embryonic stem cells it's time to make a neuron," Mandel said. The cell then triggers the expression of an ensemble of genes that coordinates nervous system development by removing REST in three distinct phases, ending with shutting down the REST gene.

"The cell gets rid of all the excess protein, kicks it off the DNA, then stomps on its head so it can't make RNA," Mandel said. "We can't detect REST in the terminally differentiated neuron." But some molecular partners of REST remain, perhaps fine-tuning gene expression in mature neurons, she said.

REST seems to work globally, binding to the starting points of as many as 1,000 genes at once. The gradual loss of REST in differentiating neurons probably orchestrates a precise sequence of genes sensitive to different levels of REST, Mandel speculates.

REST has been a difficult gene to study. Using knockout technology -- a popular technique f
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Source:Howard Hughes Medical Institute