Methyl-CpG-binding protein 2 is localized in the postsynaptic compartment: an immunochemical study of subcellular fractions.
Methyl-CpG-binding protein 2 is a characteristic member of the methyl-CpG-binding protein family of transcription regulators. In conjunction with Sin3, MeCP2 recruits class I histone deacetylases to methyl-CpG regions to suppress transcription. Rett syndrome, a disorder characterized by mental retardation and autistic features, is associated in a majority of cases with mutations within the coding region of the MeCP2 gene. Considering that defective MeCP2 has mainly been related to Rett syndrome and other neurologic manifestations, we examined methyl-CpG-binding protein 2 cellular and subcellular compartmentalization in normal brain by immunochemical methods. Methyl-CpG-binding protein 2 immunoreactivity is present mainly in neurons; while the few immunostained glia show label confined to nuclei, many neurons also show slight perikaryal staining. Using well-characterized tissue fractions, we found that methyl-CpG-binding protein 2 but not Sin3 is found in both nuclear and postsynaptic compartments. This novel extranuclear localization is not unique to methyl-CpG-binding protein 2, since it has been previously reported for other transcription regulators such as c-Fos. These findings support the concept that methyl-CpG-binding protein 2 may link synaptic activity and transcriptional regulation in neurons.
Aber
K M
KM
Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, USA.
Nori
P
P
MacDonald
S M
SM
Bibat
G
G
Jarrar
M H
MH
Kaufmann
W E
WE
D001923:Brain Chemistry; D002467:Cell Nucleus / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D003593:Cytoplasm / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006655:Histone Deacetylases; D006801:Humans; D007150:Immunohistochemistry; D051783:Methyl-CpG-Binding Protein 2; D009154:Mutation; D009457:Neuroglia / Q000737:chemistry; D009474:Neurons / Q000737:chemistry*; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000032:analysis
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D006655:Histone Deacetylases