Role of Mecp2 in Experience-Dependent Epigenetic Programming

Genes

Dietmar Spengler¹  Florian Raabe¹  Christoph A. Zimmermann¹  Anke Hoffmann¹ 

[1] Max Planck Institute of Psychiatry, Translational Research, Kraepelinstr. 2-10,Munich 80804, Germany;

关键词: early-life stress;    Mecp2;    HPA axis;    epigenetic programming;    Avp;    Crh;    Pomc;   

DOI  :  10.3390/genes6010060

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown