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

Xinsheng Nan, Jianghui Hou, Alan Maclean, Jamal Nasir, Maria Rose Lafuente, Xinhua Shu, Skirmantas Kriaucionis, Adrian Bird

Research output: Contribution to journalArticle

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 (a-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.
Original languageEnglish
Pages (from-to)2709-2714
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number8
Early online date12 Feb 2007
DOIs
Publication statusPublished - 20 Feb 2007

    Fingerprint

Keywords

  • DNA methylation
  • Rett syndrome
  • X-linked mental retardation

Cite this

Nan, X., Hou, J., Maclean, A., Nasir, J., Lafuente, M. R., Shu, X., Kriaucionis, S., & Bird, A. (2007). Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation. Proceedings of the National Academy of Sciences of the United States of America, 104(8), 2709-2714. https://doi.org/10.1073pnas.0608056104