Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function
Name
Tao-2009-Phosphorylation of M.pdf
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Author(s)
Tao, Jifang
Hu, Keping
Chang, Qiang
Wu, Hao
Sherman, Nicholas E.
Martinowich, Keri
Klose, Robert J.
Schanen, Carolyn
Jaenisch, Rudolf
Wang, Weidong
Date Issued
February 2009
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
Tao, Jifang et al. “Phosphorylation of MeCP2 at Serine 80 regulates its chromatin association and neurological function.” Proceedings of the National Academy of Sciences 106.12 (2009): 4882-4887.
Version
Final published version
Abstract
Mutations of MECP2 (Methyl-CpG Binding Protein 2) cause Rett syndrome. As a chromatin-associated multifunctional protein, how MeCP2 integrates external signals and regulates neuronal function remain unclear. Although neuronal activity-induced phosphorylation of MeCP2 at serine 421 (S421) has been reported, the full spectrum of MeCP2 phosphorylation together with the in vivo function of such modifications are yet to be revealed. Here, we report the identification of several MeCP2 phosphorylation sites in normal and epileptic brains from multiple species. We demonstrate that serine 80 (S80) phosphorylation of MeCP2 is critical as its mutation into alanine (S80A) in transgenic knock-in mice leads to locomotor deficits. S80A mutation attenuates MeCP2 chromatin association at several gene promoters in resting neurons and leads to transcription changes of a small number of genes. Calcium influx in neurons causes dephosphorylation at S80, potentially contributing to its dissociation from the chromatin. We postulate that phosphorylation of MeCP2 modulates its dynamic function in neurons transiting between resting and active states within neural circuits that underlie behaviors.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1073/pnas.0811648106
