Autism Vox

Repression and Activation of the MeCP2 Gene and Rett Syndrome

by Kristina Chew, PhD on June 2nd, 2008

Mutations in the MeCP2 gene are known to cause Rett Syndrome, which causes impairments in language and cognitive and fine motor skills; according to the International Rett’s Syndrome Foundation, Rett Syndrome is often misdiagnosed as autism. Scientists have previously thought that the MeCP2 gene repressed other genes—switching them “off”; a study published in the June 1st Science shows that it also activates—-turns “on”—-a number of other genes. While Rett Syndrome occurs almost exclusively in girls, duplications of the MeCP2 gene cause Rett-like symptoms in boys along with (in some cases) severe mental retardation.

The lead author of the study is Huda Zoghbi, M.D., a professor at Baylor College of Medicine in Houston and an investigator of the Howard Hughes Medical Institute. Dr. Zoghbi also led the team that first linked deficiencies in the MeCP-2 gene to Rett’s Syndrome. From Science Daily:

[Dr. Zoghbi] and her team analyzed gene activity patterns in the brains of mice with a MECP2 deficiency and in mice with a MECP2 duplication (MECP2+). Previous studies had revealed only subtle differences between the brains of normal and MECP2-mutant mice, but those studies measured gene activity throughout the brain. Dr. Zoghbi’s group focused on a brain region called the hypothalamus, which is known to produce hormones that influence growth, mood, and the sleep-wake cycle — all of which typically become derailed in Rett syndrome.

Their analysis revealed nearly 2600 genes that are misregulated in both mouse models, with opposite patterns. The activity of about 2200 genes dropped in MECP2-deficient mice and spiked in MECP2+ mice, indicating that MECP2 is an activator for those genes. About 400 genes showed the reverse pattern, indicating that MECP2 is a repressor for those genes.

In other experiments, the researchers confirmed that the MeCP2 protein binds directly to several of the target genes. They also found evidence that MeCP2 collaborates with another protein known to serve as a gene activator. Among the genes activated by MeCP2, the researchers found many that encode neuropeptides, proteins that are secreted by nerve cells.

Researchers hope to design therapies for Rett syndrome and for MECP2 duplication syndrome by honing in on the MeCP2 target genes (go here to read about the possibility of a genetic test for Rett’s Syndrome).

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POSTED IN: Genetics, Neuroscience, rett's syndrome