Journal ArticleDOI
The Role of MeCP2 in the Brain
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TLDR
Two alternative views of MeCP2 in the brain are considered: as a regulator of brain development or as a factor that helps maintain neuronal/glial function.Abstract:
Methyl-CpG binding protein 2 (MeCP2) was first identified in 1992 as a protein that binds specifically to methylated DNA. Mutations in the MECP2 gene were later found to be the cause of an autism spectrum disorder, Rett syndrome. Despite almost 20 years of research into the molecular mechanisms of MeCP2 function, many questions are yet to be answered conclusively. This review considers several key questions and attempts to evaluate the current state of evidence. For example, is MeCP2 just a methyl-CpG binding protein? Is it a multifunctional protein or primarily a transcriptional repressor? We also consider whether MeCP2, as a chromosome-binding protein, acts at specific sites within the genome or more globally, and in which cell types it is functionally important. Finally, we consider two alternative views of MeCP2 in the brain: as a regulator of brain development or as a factor that helps maintain neuronal/glial function.read more
Citations
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Interneuron dysfunction in psychiatric disorders
TL;DR: In conclusion, animal models demonstrate that the molecular basis of disruption is linked to specific defects in the development and function of interneurons — the cells that are responsible for establishing inhibitory circuits in the brain.
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Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders.
Sacha B. Nelson,Vera Valakh +1 more
TL;DR: The contrasting evidence for primary defects in inhibition or excitation in ASDs is explored and the findings are integrated in terms of the brain's ability to maintain functional homeostasis.
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From the genetic architecture to synaptic plasticity in autism spectrum disorder
TL;DR: Genetics studies of autism spectrum disorder (ASD) have identified several risk genes that are key regulators of synaptic plasticity, and when deleterious mutations occur, inefficient genetic buffering and impaired synaptic homeostasis may increase an individual's risk for ASD.
Journal ArticleDOI
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.
Journal ArticleDOI
Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain
Junjie U. Guo,Yijing Su,Joo Heon Shin,Jaehoon Shin,Hongda Li,Bin Xie,Chun Zhong,Shaohui Hu,Thuc T Le,Guoping Fan,Heng Zhu,Qiang Chang,Yuan Gao,Guo Li Ming,Hongjun Song +14 more
TL;DR: The characteristics of CpH methylation suggest that a substantially expanded proportion of the neuronal genome is under cytosine methylation regulation and provide a new foundation for understanding the role of this key epigenetic modification in the nervous system.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
Xinsheng Nan,Huck-Hui Ng,Colin A. Johnson,Carol D. Laherty,Bryan M. Turner,Robert N. Eisenman,Adrian Bird +6 more
TL;DR: The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2, an abundant nuclear protein that is essential for mouse embryogenesis.
Journal ArticleDOI
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription.
Peter L. Jones,Gert C. Jan Veenstra,Paul A. Wade,Danielle Vermaak,Stefan U. Kass,Nicoletta Landsberger,John Strouboulis,Alan P. Wolffe +7 more
TL;DR: The results establish a direct causal relationship between DNA methylation-dependent transcriptional silencing and the modification of chromatin.
Journal ArticleDOI
Regional differences in synaptogenesis in human cerebral cortex.
TL;DR: Findings in the human resemble those in rhesus monkeys, including overproduction of synaptic contacts in infancy, persistence of high levels of synaptic density to late childhood or adolescence, the absolute values of maximum and adult synaptic density, and layer specific differences.
Journal ArticleDOI
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.