Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 8, Pages 2709-2714Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0608056104
Keywords
DNA methylation; Rett syndrome; X-linked mental retardation
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Funding
- Medical Research Council [MC_U127584475] Funding Source: researchfish
- MRC [MC_U127584475] Funding Source: UKRI
- Medical Research Council [MC_U127584475] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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 SW12/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.
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