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XB-ART-4580
Mol Cell August 1, 2003; 12 (2): 425-35.

A mutant form of MeCP2 protein associated with human Rett syndrome cannot be displaced from methylated DNA by notch in Xenopus embryos.

Stancheva I , Collins AL , Van den Veyver IB , Zoghbi H , Meehan RR .


Abstract
MeCP2 is a DNA binding protein that represses transcription of methylated genes in vitro, but the endogenous function of MeCP2 in vivo is unclear. Here, we demonstrate that in Xenopus laevis embryos MeCP2 is a partner of the SMRT corepressor complex that regulates the expression of a neuronal repressor xHairy2a in differentiating neuroectoderm. The MeCP2/SMRT complex is bound to the promoter of the silenced xHairy2a gene and is displaced upon activation by the Notch intracellular domain (NICD). A truncated form of MeCP2 (R168X) found in patients with Rett syndrome cannot interact with the SMRT complex or fully activate xHairy2a during primary neurogenesis. This disruption of MeCP2 activity results in abnormal patterning of primary neurons during neuronal differentiation. Our results support a model whereby the dynamic association of MeCP2 with methylated DNA and the SMRT complex regulates a gene involved in cell fate decisions during primary neurogenesis in Xenopus.

PubMed ID: 14536082
Article link: Mol Cell
Grant support: [+]
Genes referenced: acta4 actc1 actl6a dll1 dnmt1 ecd esr-5 gast hdac1 hes4 hes5.1 hes7.2 isyna1 mecp2 ncam1 ncor2 neurod1 neurog1 neurog2 notch1 odc1 pcna rbpj sin3a smo tub tubb2b
Morpholinos: mecp2 MO1 sin3a MO1

Disease Ontology terms: drug-induced mental disorder
OMIMs: RETT SYNDROME; RTT [+]

Article Images: [+] show captions


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