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Officials last week revealed that the U.S. contribution to ITER could cost $3.9 billion by 2034—roughly four times the...
An experimental hepatitis B drug that looked safe in animal trials tragically killed five of 15 patients in 1993. Now,...
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Astronomers have discovered an Earth-sized planet in the habitable zone of a red dwarf—a star cooler than the sun—500...
Three years ago, Jennifer Francis of Rutgers University proposed that a warming Arctic was altering the behavior of the...
- 17 April 2014 12:48 pm , Vol. 344 , #6181
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When Genes Are Out of the Loop
21 December 2004 (All day)
A defective protein has long been suspected in helping trigger Rett syndrome, a neurological disorder that strikes girls and is characterized by autistic-like behaviors, severe loss of motor control, breathing irregularities, and bone problems. Now scientists have discovered that, at least in mice, the pernicious protein may fail in its task of helping to loop a stretch of DNA, altering activity of another key protein.
In girls afflicted with Rett syndrome, symptoms usually emerge after about 18 months of seemingly normal development. Around five years ago, scientists linked the disease to mutations in a gene on the X chromosome known as MECP2, which is in charge of turning other genes on and off. To better understand the gene's effects, a team led by molecular biologist Terumi Kohwi-Shigematsu of the Lawrence Berkeley National Laboratory in California compared the activity of a range of genes in normal mice and in mice without a working MECP2 gene. In the latter group, the gene DLX5 was dialed way up, making almost double the normal amount of protein. Only one copy of DLX5 is usually turned on in human cells, but the extra activity suggested both copies were turned on. But how MECP2 made this happen wasn't clear.
To find out, the scientists developed a method for spying on how the DNA encoding DLX5 was folded up in the mouse cells. DNA is usually tightly bound up in proteins and RNA, together known as chromatin, and when the cell needs access to particular genes, it has to unwind this chromatin. The researchers discovered that MECP2 is required for looping certain areas of chromatin; in mice without a working MECP2 gene, a loop was missing, relaxing the control of DLX5 and possibly other genes, the researchers report online in the 19 December Nature Genetics. The findings suggest that both copies of DLX5 may be turned on when MECP2 is out of commission.
The next question is whether cranking up the DLX5 gene results in some of the problems of Rett syndrome, says Kohwi-Shigematsu. The DLX5 protein is important in synthesizing GABA, a neurotransmitter linked to other neurological disorders such as epilepsy and Parkinson's disease. The findings are an important piece in a very big puzzle, says Alan Percy of the University of Alabama at Birmingham. "With Rett syndrome you have genes that are functioning willy-nilly. It is really a multi-system involvement--We still don't know the whole story."