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Every cell in our body contains the same genes. Yet a brain cell is distinctly different from a heart cell or a liver cell. What differentiates these cells are the genes that are either silenced or active and the degree of activation of the genes, also known as expression.
Scientists have known for many years that the “Rett protein”, MeCP2, regulates the expression of other genes. The big question has been, which genes?
Michael Greenberg of Harvard University, and his lab members Harrison Gabel and Benyam Kinde, may have an answer: long genes. The journal, Nature, is publishing this finding today.
Genes are made up of nucleotides (think back to high school biology: A,T,C,G) The average gene has about 20,000 nucleotides, but some have as many as a million. The scientists in the Greenberg lab found that the MeCP2 protein acts as a dimmer switch, dampening the expression of long genes. When the MeCP2 protein is absent, as in the case of Rett, with no dimmer switch to regulate it, long gene expression goes up. Any deviation from the normal expression pattern causes problems.
From this finding, the scientists suggest that Rett Syndrome may be caused by a widespread overexpression of long genes.
You may be asking yourself, why does this matter? It matters because there is a drug that can rebalance the expression levels of long genes. The Greenberg lab has already tested this drug in cells missing the MeCP2 protein with encouraging results. Experiments are now underway to test the drug in Rett mice.
This is a promising development. We are providing the following resources to help you understand the progress being reported today.
Animation of Findings
Interview with Greenberg Lab Members
It stands to reason that in our battle to cure Rett Syndrome it would be of great benefit to understand the function of the “Rett protein”, MeCP2. Towards this end RSRT launched the MECP2 Consortium in 2011, a unique $1.8 MM collaboration between three distinguished scientists, Adrian Bird, Michael Greenberg, Gail Mandel. On June 16th the first two publications from this collaborative effort are published in Nature Neuroscience and Nature. Together these papers provide further clarification of the elusive function of the MeCP2 protein and how mutations within it contribute to Rett.
We thank Kathy and Tony Schoener whose visionary $1 MM gift made the Consortium possible. We thank all of our donors and parent organizations worldwide who support us, in particular our funding partners Rett Syndrome Research Trust UK and the Rett Syndrome Research & Treatment Foundation.
We are providing a variety of resources to help you understand the progress being reported today.
Animation of Nature Neuroscience Paper (courtesy of Jeff Canavan)
Interview with Matt Lyst, post-doc in Bird lab
Interview with Michael Greenberg and Dan Ebert,
post-doc in Greenberg lab