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Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2709-14. Epub 2007 Feb 12.

Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation.

Author information

1
Wellcome Trust Centre for Cell Biology, University of Edinburgh, The King's Buildings, Edinburgh EH9 3JR, United Kingdom. xinsheng.nan@csc.mrc.ac.uk

Abstract

Mutations in the human methyl-CpG-binding protein gene MECP2 cause the neurological disorder Rett syndrome and some cases of X-linked mental retardation (XLMR). We report that MeCP2 interacts with ATRX, a SWI2/SNF2 DNA helicase/ATPase that is mutated in ATRX syndrome (alpha-thalassemia/mental retardation, X-linked). MeCP2 can recruit the helicase domain of ATRX to heterochromatic foci in living mouse cells in a DNA methylation-dependent manner. Also, ATRX localization is disrupted in neurons of Mecp2-null mice. Point mutations within the methylated DNA-binding domain of MeCP2 that cause Rett syndrome or X-linked mental retardation inhibit its interaction with ATRX in vitro and its localization in vivo without affecting methyl-CpG binding. We propose that disruption of the MeCP2-ATRX interaction leads to pathological changes that contribute to mental retardation.

PMID:
17296936
PMCID:
PMC1796997
DOI:
10.1073/pnas.0608056104
[Indexed for MEDLINE]
Free PMC Article

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