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

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.

Pubmed ID: 17296936

Authors

  • Nan X
  • Hou J
  • Maclean A
  • Nasir J
  • Lafuente MJ
  • Shu X
  • Kriaucionis S
  • Bird A

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

February 20, 2007

Associated Grants

  • Agency: Medical Research Council, Id: MC_U127584475
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Animals
  • Brain
  • Cells, Cultured
  • DNA
  • DNA Helicases
  • DNA Methylation
  • Humans
  • Intellectual Disability
  • Methyl-CpG-Binding Protein 2
  • Mice
  • Mutation
  • Nuclear Proteins
  • Protein Binding
  • Protein Transport
  • Two-Hybrid System Techniques