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

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.

• Authors: Xinsheng Nan, Jianghui Hou, Alan Maclean, Jamal Nasir, Maria Jose Lafuente, Xinhua Shu, Skirmantas Kriaucionis, Adrian Bird
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 104 Issue 8 Pg. 2709-14 (Feb 20 2007) ISSN: 0027-8424 [Print] United States
• PMID: 17296936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Methyl-CpG-Binding Protein 2
• Nuclear Proteins
• DNA
• DNA Helicases
• ATRX protein, human
• Atrx protein, mouse
• X-linked Nuclear Protein

Topics

• Animals
• Brain (cytology, metabolism)
• Cells, Cultured
• DNA (metabolism)
• DNA Helicases (chemistry, metabolism)
• DNA Methylation
• Humans
• Intellectual Disability (genetics)
• Methyl-CpG-Binding Protein 2 (deficiency, genetics, metabolism)
• Mice
• Mutation (genetics)
• Nuclear Proteins (chemistry, metabolism)
• Protein Binding
• Protein Transport
• Two-Hybrid System Techniques
• X-linked Nuclear Protein