title: Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action.
abstract: Rett syndrome (RTT) is a devastating genetic disorder that worldwide represents the most common genetic cause of severe intellectual disability in females. Most cases are caused by mutations in the X-linked MECP2 gene. Several recent studies have demonstrated that RTT mimicking animal models do not develop an irreversible condition and phenotypic rescue is possible. However, no cure for RTT has been identified so far, and patients are only given symptomatic and supportive treatments. The development of clinical applications imposes a more comprehensive knowledge of MeCP2 functional role(s) and their relevance for RTT pathobiology. Herein, we thoroughly survey the knowledge about MeCP2 structure and functions, highlighting the necessity of identifying more functional domains and the value of molecular genetics. Given that, in our opinion, RTT ultimately is generated by perturbations in gene transcription and so far no genes/pathways have been consistently linked to a dysfunctional MeCP2, we have used higher-level bioinformatic analyses to identify commonly deregulated mechanisms in MeCP2-defective samples. In this review we present our results and discuss the possible value of the utilized approach.
authors.affiliation: San Raffaele Rett Research Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy; Laboratory of Genetic and Epigenetic Control of Gene Expression, Department of Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, Busto Arsizio 21052, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bedogni
authors.affiliation: Fondazione Istituto Nazionale Genetica Molecolare, Milan 20122, Italy.
authors.forename: Riccardo L
authors.initials: RL
authors.lastname: Rossi
authors.affiliation: San Raffaele Rett Research Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
authors.affiliation: San Raffaele Rett Research Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy; Laboratory of Genetic and Epigenetic Control of Gene Expression, Department of Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, Busto Arsizio 21052, Italy.
authors.forename: Clementina
authors.initials: C
authors.lastname: Cobolli Gigli
authors.affiliation: San Raffaele Rett Research Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy; Laboratory of Genetic and Epigenetic Control of Gene Expression, Department of Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, Busto Arsizio 21052, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Gandaglia
authors.affiliation: Laboratory of Genetic and Epigenetic Control of Gene Expression, Department of Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, Busto Arsizio 21052, Italy.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kilstrup-Nielsen
authors.affiliation: San Raffaele Rett Research Center, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy; Laboratory of Genetic and Epigenetic Control of Gene Expression, Department of Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, Busto Arsizio 21052, Italy. Electronic address: landsben@uninsubria.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Landsberger
mesh_terms: D000818:Animals; D019295:Computational Biology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism*; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D051783:Methyl-CpG-Binding Protein 2
keywords: MeCP2; Molecular genetics; Pathway enrichment analysis; Perturbation in gene expression; Rett syndrome; Structure and function