The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a 'code' affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability.
Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails.
Journal of the American Academy of Child and Adolescent Psychiatry
OBJECTIVE: Child and adolescent psychiatry is rife with examples of the sustained effects of early experience on brain function. The study of behavioral genetics provides evidence for a relation between genomic variation and personality and with the risk for psychopathology. A pressing challenge is that of conceptually integrating findings from genetics into the study of personality without regressing to arguments concerning the relative importance of genomic variation versus nongenomic or environmental influences.
Alterations in histone lysine methylation and other epigenetic regulators of gene expression contribute to changes in brain transcriptomes in mood and psychosis spectrum disorders, including depression and schizophrenia. Genetic association studies and animal models implicate multiple lysine methyltransferases and demethylases in the neurobiology of emotion and cognition.
Less than 2% of the 80-90% heritability of major psychiatric disease, for example, schizophrenia and manic-depressive illness is attributable to genes identified by linkage and association. Where is the missing heritability? The recently described PRDM9 gene imposes epigenetic stability on the XY body in male meiosis including Sapiens-specific variation relating to a gene pair (Protocadherin11XY) created by X to Y duplication at 6MYA.
The International Journal of Neuropsychopharmacology
The synapsin family of neuronal phosphoproteins is composed of three genes (SYN1, SYN2 and SYN3) with alternative splicing resulting in a number of variants with various levels of homology. These genes have been postulated to play significant roles in several neuropsychiatric disorders, including bipolar disorder, schizophrenia and epilepsy. Epigenetic regulatory mechanisms, such as histone modifications in gene regulatory regions, have also been proposed to play a role in a number of psychiatric disorders, including bipolar disorder and major depressive disorder.
OBJECTIVE: Epigenetic changes are stable and long-lasting chromatin modifications that regulate genomewide and local gene activity. The addition of two methyl groups to the 9th lysine of histone 3 (H3K9me2) by histone methyltransferases (HMT) leads to a restrictive chromatin state, and thus reduced levels of gene transcription. Given the numerous reports of transcriptional down-regulation of candidate genes in schizophrenia, we tested the hypothesis that this illness can be characterized by a restrictive epigenome.
Alzheimer' s disease (AD) is the most common form of dementia causing an increasing emotional and economical burden to our societies. Although much progress has been made regarding the molecular mechanisms that underlie AD pathogenesis effective therapies are not available yet. The emerging field of neuroepigenetics has provided evidence that de-regulation of epigenetic processes play a role in AD.
Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
The growing list of mutations implicated in monogenic disorders of the developing brain includes at least seven genes (ARX, CUL4B, KDM5A, KDM5C, KMT2A, KMT2C, KMT2D) with loss-of-function mutations affecting proper regulation of histone H3 lysine 4 methylation, a chromatin mark which on a genome-wide scale is broadly associated with active gene expression, with its mono-, di- and trimethylated forms differentially enriched at promoter and enhancer and other regulatory sequences.
When compared to women, men have a higher incidence of schizophrenia, with increases in negative and cognitive symptoms, and an overall poorer disease course. Schizophrenia is conceptualized as a disorder of aberrant gene transcription and regulation. Thus, epigenetics, the study of environmentally induced changes in gene regulation, could advance our understanding of the molecular underpinnings of schizophrenia. Peripheral histone methyltransferase (HMT) mRNA levels have been previously shown to be significantly increased in patients with schizophrenia and correlate with symptomology.