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Genes 2015, 6(1), 60-86; doi:10.3390/genes6010060

Role of Mecp2 in Experience-Dependent Epigenetic Programming

Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10, Munich 80804, Germany
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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)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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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