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Genes 2015, 6(1), 60-86;

Role of Mecp2 in Experience-Dependent Epigenetic Programming

Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10, Munich 80804, Germany
Author to whom correspondence should be addressed.
Academic Editor: J. Peter W. Young
Received: 24 November 2014 / Revised: 18 February 2015 / Accepted: 28 February 2015 / Published: 6 March 2015
(This article belongs to the Section Molecular Genetics and Genomics)
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Mutations 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
Keywords: early-life stress; Mecp2; HPA axis; epigenetic programming; Avp; Crh; Pomc early-life stress; Mecp2; HPA axis; epigenetic programming; Avp; Crh; Pomc

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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.

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