title: Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway.
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.
authors.affiliation: 1] Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA [2] Genetics Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Hongda
authors.initials: H
authors.lastname: Li
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Chau
authors.affiliation: University of New Mexico, Albuquerque, New Mexico 87131, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Santistevan
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Weixiang
authors.initials: W
authors.lastname: Guo
authors.affiliation: McArdle Laboratory, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Kong
authors.affiliation: Institute of Genetics, College of Life Sciences, Zhejiang University, Zhejiang 310058, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Mitul
authors.initials: M
authors.lastname: Kadakia
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Masliah
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Chi
authors.affiliation: Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 1] Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA [2] Genetics Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA [3] Department of Neurology, University of Wisconsin-Madison, Madison, Wisconsin 53705, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chang
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D051880:Receptors, Notch; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B