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Mechanisms of Rett Syndrome

Rett Syndrome symptoms can be associated with the failure of mutated MECP2 to regulate transcription of a specific gene, DLX5, one allele of which is normally imprinted. Without the MeCP2 protein, production of the Dlx5 protein is increased, which must influence production of the neurotransmitter GABA and may also affect the expression of other, related genes in the DLX family with consequences for the development of the brain.

Absent or defective MeCP2 allows increased expression of the DLX5 gene through the loss of a loop of silent chromatin, and the activation of additional neighboring chromatin. This dramatic rearrangement in the DLX5/6 gene neighborhood may also involve other disturbances in gene expression. Similar rearrangements, with equally profound effects, may be found among the five dozen other genes targeted in the brain by MeCP2, which are now under active investigation by Kohwi-Shigematsu and her colleagues.

"Loss of silent chromatin looping and impaired imprinting of DLX5 in Rett syndrome," by Shin-ichi Horike, Shutao Cai, Masaru Miyano, Jan-Fang Chen, and Terumi Kohwi-Shigematsu, appears in advance online publication of the January issue of Nature Genetics. [See http://origin.www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/vaop/ncurrent/index.html]

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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
19-Dec-2004