Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway

Hongda Li, Xiaofen Zhong, Kevin F. Chau, Nicholas J. Santistevan, Weixiang Guo, Guangyao Kong, Xuekun Li, Mitul Kadakia, Jamie Masliah, Jingyi Chi, Peng Jin, Jing Zhang, Xinyu Zhao and Qiang Chang ()
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Hongda Li: Waisman Center, University of Wisconsin–Madison
Xiaofen Zhong: Waisman Center, University of Wisconsin–Madison
Kevin F. Chau: Waisman Center, University of Wisconsin–Madison
Nicholas J. Santistevan: University of New Mexico
Weixiang Guo: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
Guangyao Kong: McArdle Laboratory, University of Wisconsin–Madison
Xuekun Li: Institute of Genetics, College of Life Sciences, Zhejiang University
Mitul Kadakia: Waisman Center, University of Wisconsin–Madison
Jamie Masliah: Waisman Center, University of Wisconsin–Madison
Jingyi Chi: Waisman Center, University of Wisconsin–Madison
Peng Jin: Emory University
Jing Zhang: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
Xinyu Zhao: Waisman Center, University of Wisconsin–Madison
Qiang Chang: Waisman Center, University of Wisconsin–Madison

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian brain. However, it is unknown whether phosphorylation at any of the previously identified sites on MeCP2 can be induced by signals other than neuronal activity in other cell types, and what functions MeCP2 phosphorylation may have in those contexts. Here we show that in neural progenitor cells isolated from the adult mouse hippocampus, cell cycle-linked phosphorylation at serine 421 on MeCP2 is directly regulated by aurora kinase B and modulates the balance between proliferation and neural differentiation through the Notch signalling pathway. Our findings suggest MeCP2 S421 phosphorylation may function as a general epigenetic switch accessible by different extracellular stimuli through different signalling pathways for regulating diverse biological functions in different cell types.

Date: 2014
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DOI: 10.1038/ncomms6601

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