Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function
Xinyu Zhao,Tetsuya Ueba,Tetsuya Ueba,Brian R. Christie,Basam Z. Barkho,Michael J. McConnell,Kinichi Nakashima,Edward S. Lein,Brennan D. Eadie,Andrew R. Willhoite,Alysson R. Muotri,Robert G. Summers,Jerold Chun,Kuo-Fen Lee,Fred H. Gage +14 more
TL;DR: It is found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability, which indicates that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions.
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Abstract: DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here we report the generation and analysis of MBD1-/- mice. MBD1-/- mice had no detectable developmental defects and appeared healthy throughout life. However, we found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. Furthermore, adult MBD1-/- mice had decreased neurogenesis, impaired spatial learning, and a significant reduction in long-term potentiation in the dentate gyrus of the hippocampus. Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions.
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Methyl-CpG binding proteins in the nervous system
Guoping Fan,Leah Hutnick +1 more
TL;DR: This mini-review summarizes the recent advances in studying the diverse functions of MeCP2 as a prototype for other methyl-CpG binding proteins in the development and function of the vertebrate nervous system.
Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells
TL;DR: A discussion of what might be the function of newly generated neurons in the adult brain, and a summary of present thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease are provided.
•Dissertation
Biochemical analysis of MBD1
Matthew James Lyst
- 01 Jan 2009
TL;DR: The proton of proton and release of enzyme by β-elimination 5-methylcytosine (reaction product) is characterized by X-ray diffraction and Na6(CO3)(SO4)2(SO3)2, where Na2SO4 is the proton determinant and Na2CO3 is the restriction substance.
RNA-Binding Protein FXR2 Regulates Adult Hippocampal Neurogenesis by Reducing Noggin Expression
Weixiang Guo,Li Zhang,Devin M. Christopher,Zhao-Qian Teng,Sarah R. Fausett,Chang-Mei Liu,Olivia L. George,John Klingensmith,Peng Jin,Xinyu Zhao +9 more
TL;DR: It is shown that the RNA-binding protein FXR2 specifically regulates DG neurogenesis by reducing the stability of Noggin mRNA, which leads to increased Noggins expression and subsequently reduced BMP signaling, which results in increased proliferation and altered fate specification of neural stem/progenitor cells in DG.
DNA methylation 40 years later: Its role in human health and disease.
Maria Irene Scarano,Maria Irene Scarano,Maria Strazzullo,Maria R. Matarazzo,Maurizio D'Esposito +4 more
TL;DR: The impact of the studies on DNA methylation, the “primadonna” in the epigenetic scenario, on the understanding of basic phenomena, such as X inactivation and genomic imprinting is reviewed.
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