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J Child Neurol. 2003 Oct;18(10):675-82.

MeCP2 expression in human cerebral cortex and lymphoid cells: immunochemical characterization of a novel higher-molecular-weight form.

Author information

1
Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Most cases of Rett syndrome are associated with mutations in the coding region of MECP2. Here we characterized a novel MeCP2 immunoreactivity, initially detected in normal cerebral cortex, by using a panel of MeCP2 antibodies and a combination of immunochemical techniques. We found that a novel higher-molecular-weight form (approximately 100 kDa) of MeCP2 is detected in human frontal cortex nuclear and synaptic fractions and in lymphoid cells. Although in the cortex the higher-molecular-weight form is relatively more abundant than the standard approximately 75 kDa immunoreactivity, in extranuclear locations, lymphocyte lysates show a predominance of the standard 75 kDa band. Lymphoblasts revealed a more complex pattern of MeCP2 expression, with prominent higher-molecular-weight form and both higher-molecular-weight form and 75 kDa MeCP2 immunoreactivities encompassing several closely migrating bands. We also successfully immunoprecipitated both the 75 kDa immunoreactivity and the higher-molecular-weight form MeCP2 from cerebral cortex with a C-terminal antibody and confirmed their identities by immunoblotting with C- and N-terminal antibodies. Our data provide compelling evidence for the existence of a novel MeCP2 molecular form, most likely the result of post-translational modification. Detection in both brain and lymphoid cells suggests an important role for higher-molecular-weight form in MeCP2-dependent processes. The presence of higher-molecular-weight form MeCP2 in postsynaptic fractions indicates a possible involvement in linking synaptic activity and transcriptional repression that, in turn, could play a role in the pathogenesis of Rett syndrome and other neurologic disorders.

PMID:
14649548
DOI:
10.1177/08830738030180101001
[Indexed for MEDLINE]

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