MeCP2 expression in human cerebral cortex and lymphoid cells: Immunochemical characterization on a novel higher-molecular-weight form

Mohammed H. Jarrar, Charles G. Danko, Sriram Reddy, Ye Jin M. Lee, Genila Bibat, Walter E. Kaufmann

Research output: Contribution to journalArticlepeer-review

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 (- 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 - 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 disorderd.

Original languageEnglish (US)
Pages (from-to)675-682
Number of pages8
JournalJournal of child neurology
Volume18
Issue number10
DOIs
StatePublished - Oct 2003

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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