Role of Mecp2 in Experience-Dependent Epigenetic Programming
AbstractMutations in the X-linked gene MECP2, the founding member of a family of proteins recognizing and binding to methylated DNA, are the genetic cause of a devastating neurodevelopmental disorder in humans, called Rett syndrome. Available evidence suggests that MECP2 protein has a critical role in activity-dependent neuronal plasticity and transcription during brain development. Moreover, recent studies in mice show that various posttranslational modifications, notably phosphorylation, regulate Mecp2’s functions in learning and memory, drug addiction, depression-like behavior, and the response to antidepressant treatment. The hypothalamic-pituitary-adrenal (HPA) axis drives the stress response and its deregulation increases the risk for a variety of mental disorders. Early-life stress (ELS) typically results in sustained HPA-axis deregulation and is a major risk factor for stress related diseases, in particular major depression. Interestingly, Mecp2 protein has been shown to contribute to ELS-dependent epigenetic programming of Crh, Avp, and Pomc, all of these genes enhance HPA-axis activity. Hereby ELS regulates Mecp2 phosphorylation, DNA binding, and transcriptional activities in a tissue-specific and temporospatial manner. Overall, these findings suggest MECP2 proteins are so far underestimated and have a more dynamic role in the mediation of the gene-environment dialog and epigenetic programming of the neuroendocrine stress system in health and disease. View Full-Text
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Zimmermann, C.A.; Hoffmann, A.; Raabe, F.; Spengler, D. Role of Mecp2 in Experience-Dependent Epigenetic Programming. Genes 2015, 6, 60-86.
Zimmermann CA, Hoffmann A, Raabe F, Spengler D. Role of Mecp2 in Experience-Dependent Epigenetic Programming. Genes. 2015; 6(1):60-86.Chicago/Turabian Style
Zimmermann, Christoph A.; Hoffmann, Anke; Raabe, Florian; Spengler, Dietmar. 2015. "Role of Mecp2 in Experience-Dependent Epigenetic Programming." Genes 6, no. 1: 60-86.