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.
read more
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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Role of Epigenetics in the Brain
Stephanie Matt,Eric D. Roth,Tania L. Roth +2 more
- 01 Jan 2014
TL;DR: Key studies demonstrating a role for epigenetic mechanisms in these phenomena, including changes in phenotypes that are passed on to the next generation, gene imprinting, neural cell differentiation, neurogenesis, cognition, and the susceptibility to stress-related disorders are highlighted.
5
Characterization of a Mouse Model of Börjeson-Forssman-Lehmann Syndrome
Raies Ahmed
- 26 Feb 2019
TL;DR: It is shown that the mutation drastically reduced Phf6 transcript levels and produced a truncated protein at very low levels in the developing brain of mutant mice, a rare X-linked intellectual disability disorder characterized by large ears, truncal obesity, and long tapering fingers.
Adult Neural Stem Cell Multipotency and Differentiation Are Directed by the Methyl-CpG-Binding Protein MBD1.
Elad Lax,Daniel M Sapozhnikov +1 more
TL;DR: The generation of new neurons in the subventricular zone of the dentate gyrus during adulthood is indispensable to hippocampal-dependent learning and memory formation and a decrease in neurogenesis is associated with increased anxiety, depression, and other problems.
4
Astrocyte-derived soluble factors promoting neuronal differentiation of adult neural progenitor cells
Jisun Oh
- 01 Jan 2010
TL;DR: This paper presents a meta-analysis of determinants of neurological differentiation in adults and young people using a model derived from HIPPOCAMPUS and a comparison of apples to apples.
4
References
DNA methylation patterns and epigenetic memory
TL;DR: The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development.
Mammalian neural stem cells.
TL;DR: Before the full potential of neural stem cells can be realized, the authors need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells.
5K
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.
4.2K
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.