Human Molecular Genetics Advance Access originally published online on January 27, 2009
Human Molecular Genetics 2009 18(8):1415-1423; doi:10.1093/hmg/ddp048
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MeCP2 involvement in the regulation of neuronal 
-tubulin production
Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Ein Kerem, Jerusalem 91120, Israel
* To whom correspondence should be addressed. Tel: +972 26758172; Fax: +972 26415848; Email: razina{at}cc.huji.ac.il
Received January 5, 2009; Revised January 5, 2009; Accepted January 23, 2009
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a dominant mutation in the X-linked methyl CpG binding protein 2 (MeCP2) gene. Neuroanatomically, RTT is characterized by a reduction in dendritic arborization and perikaryal size in the brain. MECP2 binds methylated promoters and facilitates assembly of a multiprotein repressor complex that includes Sin3A and the histone deacetylases HDAC1/HDAC2. MeCP2 has recently been found to be downregulated in autistic spectrum disorders such as Angelman syndrome (AS) and RTT, which share some phenotypic manifestations. We have conducted expression analysis of cytoskeleton-related genes in brain tissue of RTT and AS patients. Striking examples of genes with reduced expression were TUBA1B and TUBA3 that encode the ubiquitous 
-tubulin and the neuronal specific -tubulin, respectively. In accordance with the downregulation of expression of these genes, we have observed a reduction in the level of the corresponding protein product—tyrosinated -tubulin. Low levels of -tubulin and deteriorated cell morphology were also observed in MeCP2–/y MEF cells. The effects of MeCP2 deficiency in these cells were completely reversed by introducing and expressing the human MeCP2 gene. These results imply that MeCP2 is involved in the regulation of neuronal -tubulin and add molecular evidence that reversal of the effects of MeCP2 deficiency is achievable. This raises hopes for a cure of Rett syndrome and related MeCP2 deficiency disorders of the autistic spectrum.