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 are involved in restricting differentiation plasticity in neurons
Hiroki Setoguchi,Masakazu Namihira,Jun Kohyama,Hirotsugu Asano,Tsukasa Sanosaka,Kinichi Nakashima +5 more
TL;DR: It is shown that late‐gestation neuroepithelial cells can still give rise to neurons and that these neurons do not respond to a STAT3‐activating cytokine to express GFAP, and that MeCP2 actually binds to the highly methylated exon 1 of the GFAP gene in neurons, suggesting that region‐specific DNA methylation and MBDs play an important role in the regulation of differentiation plasticity in neurons.
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Accumulation of mutations and somatic selection in aging neural stem/progenitor cells.
TL;DR: The retention of specific alleles for chromosomes 9 and 19 suggests that a subset of mutational events lead to an allele‐specific survival advantage within the neural stem cell compartment.
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Dynamic effects of Fto in regulating the proliferation and differentiation of adult neural stem cells of mice.
Yuhang Cao,Yuhang Cao,Yingliang Zhuang,Yingliang Zhuang,Junchen Chen,Junchen Chen,Weize Xu,Yikai Shou,Xiaoli Huang,Qiang Shu,Xuekun Li,Xuekun Li +11 more
TL;DR: An important function of Fto is revealed in regulating aNSCs through modulating Pdgfra/Socs5-Stat3 pathway and can rescue the neurogenic deficits induced by Fto depletion.
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Unmasking of epigenetically silenced candidate tumor suppressor genes by removal of methyl-CpG-binding domain proteins
Lidia Lopez-Serra,Esteban Ballestar,Santiago Ropero,Fernando Setien,Billard Lm,Mario F. Fraga,Pilar López-Nieva,Miguel Alaminos,D. Guerrero,Robert Dante,Manel Esteller +10 more
TL;DR: The results unveil new targets for epigenetic inactivation mediated by MBDs in transformed cells, such as the cell adhesion protein γ-parvin and the fibroblast growth factor 19, where their bona fide tumor suppressor features are demonstrated.
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Neonatal Maternal Separation Alters the Capacity of Adult Neural Precursor Cells to Differentiate into Neurons Via Methylation of Retinoic Acid Receptor Gene Promoter
Shuken Boku,Shuken Boku,Hiroyuki Toda,Shin Nakagawa,Akiko Kato,Takeshi Inoue,Tsukasa Koyama,Noboru Hiroi,Ichiro Kusumi +8 more
TL;DR: NMS attenuates the capacity of adult hippocampal neural precursor cells to differentiate into neurons by decreasing expression of RARα through DNMT1-mediated methylation of its promoter.
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