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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DNA methylation: dynamic and stable regulation of memory
TL;DR: This review will further illustrate the recent hypothesis that DNA methylation participates in the transcriptional regulation necessary for memory.
•Dissertation
Recherche de nouvelles protéines humaines se liant à l'ADN méthylé
Michaël Joulie
- 26 Sep 2011
TL;DR: La methylation exerce ces effets par l'intermediaire de proteines dediees, qui reconnaissent specifiquement l'ADN methyle et controlent the transcription en modulant the chromatine.
5
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Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.
Ruthie E. Amir,Ignatia B. Van den Veyver,Mimi Wan,Charles Q. Tran,Uta Francke,Huda Y. Zoghbi +5 more
TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.
TL;DR: Results indicate that while a 3-fold reduction in levels of genomic m5C has no detectable effect on the viability or proliferation of ES cells in culture, a similar reduction of DNA methylation in embryos causes abnormal development and embryonic lethality.
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The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses
TL;DR: This book aims to investigate elementary forms of learning and memory at a cellular molecular level—as specific molecular activities within identified nerve cells withinidentified nerve cells.