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The role of MeCP2 in CNS development and function 总被引:1,自引:0,他引:1
Elisa S. Na 《Hormones and behavior》2011,59(3):364-5
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Genome-wide activity-dependent MeCP2 phosphorylation regulates nervous system development and function 总被引:1,自引:0,他引:1
Cohen S Gabel HW Hemberg M Hutchinson AN Sadacca LA Ebert DH Harmin DA Greenberg RS Verdine VK Zhou Z Wetsel WC West AE Greenberg ME 《Neuron》2011,72(1):72-85
Autism spectrum disorders such as Rett syndrome (RTT) have been hypothesized to arise from defects in experience-dependent synapse maturation. RTT is caused by mutations in MECP2, a nuclear protein that becomes phosphorylated at S421 in response to neuronal activation. We show here that disruption of MeCP2 S421 phosphorylation in?vivo results in defects in synapse development and behavior, implicating activity-dependent regulation of MeCP2 in brain development and RTT. We investigated the mechanism by which S421 phosphorylation regulates MeCP2 function and show by chromatin immunoprecipitation-sequencing that this modification occurs on MeCP2 bound across the genome. The phosphorylation of MeCP2 S421 appears not to regulate the expression of specific genes; rather, MeCP2 functions as a histone-like factor whose phosphorylation may facilitate a genome-wide response of chromatin to neuronal activity during nervous system development. We propose that RTT results in part from a loss of this experience-dependent chromatin remodeling. 相似文献
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Anna Sawicka Christian Seiser 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2014,1839(8):711-718
Systematic analysis of histone modifications has revealed a plethora of posttranslational modifications that mediate changes in chromatin structure and gene expression. Histone phosphorylation is a transient histone modification that becomes induced by extracellular signals, DNA damage or entry into mitosis. Importantly, phosphorylation of histone proteins does lead not only to the binding of specific reader proteins but also to changes in the affinity for readers or writers of other histone modifications. This induces a cross-talk between different chromatin modifications that allows the spatio-temporal control of chromatin-associated events. In this review we will summarize the progress in our current knowledge of factors sensing reversible histone phosphorylation in different biological scenarios. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. 相似文献
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The story of Rett syndrome: from clinic to neurobiology 总被引:9,自引:0,他引:9