title: Role of mecp2 in experience-dependent epigenetic programming.
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.
authors.affiliation: Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10, Munich 80804, Germany. christoph_zimmermann@psych.mpg.de.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Zimmermann
authors.affiliation: Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10, Munich 80804, Germany. hoffmann@psych.mpg.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10, Munich 80804, Germany. florian_raabe@psych.mpg.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Raabe
authors.affiliation: Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10, Munich 80804, Germany. spengler@psych.mpg.de.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Spengler