Formation of a phenotype during development of the human being may result from a specific dialogue between genes and environmental factors. Expression of particular genes is controlled not only on the transcriptional level but also on the level of accessibility of genetic information through the influence for remodelling of chromatin. We characterized Rett syndrome and its molecular basis as an example of the relation between genes and environment and their influence on epigenetic processes determining the gene expression.
Subtle alterations in synaptic function contribute to the pathophysiology associated with several neuropsychiatric diseases. Modifications in synaptic vesicle trafficking can cause frequency-dependent changes in neurotransmission, alter information coding in neural circuits, and affect long-term plasticity.
Mutations of MECP2 (methyl-CpG binding protein 2) cause Rett syndrome (RTT). Mouse genetics studies have demonstrated that the lack of functional MeCP2 in the central nervous system leads to RTT-like symptoms, which could be reversed upon MeCP2 restoration. MeCP2 recognizes methylated CpG dinucleotides and may interact with other chromatin remodeling proteins. Although traditionally thought to be a transcription repressor, MeCP2 may also be involved in transcription activation.
Methyl CpG binding protein-2 (MeCP2) is an essential epigenetic regulator in human brain development. Rett syndrome, the primary disorder caused by mutations in the X-linked MECP2 gene, is characterized by a period of cognitive decline and development of hand stereotypies and seizures following an apparently normal early infancy. In addition, MECP2 mutations and duplications are observed in a spectrum of neurodevelopmental disorders, including severe neonatal encephalopathy, X-linked mental retardation, and autism, implicating MeCP2 as an essential regulator of postnatal brain development.
Journal of the American Academy of Child and Adolescent Psychiatry
OBJECTIVE: Current research suggests that the causes of autism spectrum disorders (ASD) are multifactorial and include both genetic and environmental factors. Several lines of evidence suggest that epigenetics also plays an important role in ASD etiology and that it might, in fact, integrate genetic and environmental influences to dysregulate neurodevelopmental processes. The objective of this review is to illustrate how epigenetic modifications that are known to alter gene expression without changing primary DNA sequence may play a role in the etiology of ASD.
Acquisition and maintenance of cell fate and potential are dependent on the complex interplay of extracellular signaling, gene regulatory networks and epigenetic states. During embryonic development, embryonic stem cells become progressively more restricted along specific lineages, ultimately giving rise to the diversity of cell types in the adult mammalian organism. Recent years have seen major advances in our understanding of the mechanisms that regulate the underlying transcriptional programmes during development.
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Methyl-CpG-binding protein 2 (MeCP2) is a transcriptional regulator of gene expression that is an important epigenetic factor in the maintenance and development of the central nervous system. The neurodevelopmental disorders Rett syndrome and MECP2 duplication syndrome arise from loss-of-function and gain-of-function alterations in MeCP2 expression, respectively. Several animal models have been developed to recapitulate the symptoms of Rett syndrome and MECP2 duplication syndrome.
Rett syndrome (RTT) is an X-linked human neurodevelopmental disorder with features of autism and severe neurological dysfunction in females. RTT is caused by mutations in methyl-CpG-binding protein 2 (MeCP2), a nuclear protein that, in neurons, regulates transcription, is expressed at high levels similar to that of histones, and binds to methylated cytosines broadly across the genome. By phosphotryptic mapping, we identify three sites (S86, S274 and T308) of activity-dependent MeCP2 phosphorylation.
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social interactions, language deficits, as well as restrictive or repetitive behaviors. ASD is clinically heterogeneous with a complex etiopathogenesis which may be conceptualized as a dynamic interplay between heterogeneous environmental cues and predisposing genetic factors involving complex epigenetic mechanisms. Inherited and de novo copy number variants provide novel information regarding genes contributing to ASD.
The individual with Rett syndrome (RS) displays an array of challenging difficulties in all areas of daily living. Since there is no cure for the disorder at this moment, parents of the individual with Rett search for different interventional modalities that will improve the condition and quality of life for their child. During the last few years, many individuals with RS have experienced different kinds of interventions. This paper presents these methods with relevant case stories for others to share the possibilities.