Journal Article

MeCP2 involvement in the regulation of neuronal α-tubulin production

Liron Abuhatzira, Ruth Shemer and Aharon Razin

in Human Molecular Genetics

Volume 18, issue 8, pages 1415-1423
Published in print April 2009 | ISSN: 0964-6906
Published online January 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp048
MeCP2 involvement in the regulation of neuronal α-tubulin production

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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 α-tubulin and the neuronal specific α-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 α-tubulin. Low levels of α-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 α-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.

Journal Article.  5264 words.  Illustrated.

Subjects: Genetics and Genomics

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