Mouse models of MeCP2 disorders share gene expression changes in the cerebellum and hypothalamus
TLDR
The data suggest that either gain or loss of MeCP2 results in gene expression changes in multiple brain regions and that some of these changes are global, which might identify subsets of genes that are more amenable to manipulation, and can thus be used to modulate some of the disease phenotypes.Citations
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TETonic shift: biological roles of TET proteins in DNA demethylation and transcription
TL;DR: The recent discovery that ten-eleven translocation proteins are 5-methylcytosine oxidases has provided several chemically plausible pathways for the reversal of DNA methylation, thus triggering a paradigm shift in understanding of how changes inDNA methylation are coupled to cell differentiation, embryonic development and cancer.
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MeCP2 Binds to 5hmC Enriched within Active Genes and Accessible Chromatin in the Nervous System
TL;DR: It is reported that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions and these findings support a model in which5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.
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The Cerebellum, Sensitive Periods, and Autism
TL;DR: Evidence that the cerebellum may guide the maturation of remote nonmotor neural circuitry and influence cognitive development and it is proposed that sensitive-period disruption of such internal brain communication can account for autism's key features is reviewed.
Dissection ofthemethyl-CpG binding domainfromthe chromosomal protein MeCP2
TL;DR: In vitro footprinting indicates that MBD binding can protect a 12 nucleotide region surrounding a methyl-CpG pair, with an approximate dissociation constant of 10(-9) M.
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MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
TL;DR: In this paper, a quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo is presented.
References
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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.
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MeCP2, a key contributor to neurological disease, activates and represses transcription.
Maria H. Chahrour,Sung Yun Jung,Chad A. Shaw,Xiaobo Zhou,Stephen T. C. Wong,Jun Qin,Huda Y. Zoghbi +6 more
TL;DR: It is shown that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target, and that it can function as both an activator and a repressor of transcription.
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A mouse Mecp2-null mutation causes neurological symptoms that mimic rett syndrome
TL;DR: The overlapping delay before symptom onset in humans and mice raises the possibility that stability of brain function, not brain development per se, is compromised by the absence of MeCP2, and generates mice lacking Mecp2 using Cre-loxP technology.
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DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation.
TL;DR: It is reported that increased synthesis of brain-derived neurotrophic factor in neurons after depolarization correlates with a decrease in CpG methylation within the regulatory region of the Bdnf gene, suggesting that DNA methylation–related chromatin remodeling is important for activity-dependent gene regulation that may be critical for neural plasticity.
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A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett's syndrome: report of 35 cases.
TL;DR: The exclusive involvement of females, correlated with findings in family data analyses, suggests a dominant mutation on one X chromosome that results in affected girls and nonviable male hemizygous conceptuses.