Epigenetic Clues in Autistic Brain

Epigenetics refers to heritable and reversible modifications to DNA or chromosomes that control gene expression and phenotype without altering the genetic code. Examples of epigenetic mechanisms include X chromosome inactivation in females in which one of the two X chromosomes is epigenetically inactivated, and parental imprinting in which maternal or paternal genes are epigenetically silenced. An emerging area in the field of epigenetics is the impact of diet and environmental pollutants on epigenetic marks important for neural development. Epigenetic mechanisms are at the interface of genes and environment and are therefore attractive marks for finding clues to complex multiple etiologies of autism spectrum disorders. While genetic analyses can be performed on blood or transformed cells lines, epigenetic marks are often tissue-specific and dynamic in cell culture. Therefore, postmortem brain samples are imperative for investigating epigenetic alterations in autism. Current evidence for epigenetic alterations in autism frontal cortex includes decreased expression of two known neurodevelopmentally important genes, MECP2 and UBE3A, correlate with detectable changes in DNA methylation. Furthermore, the GABA-A receptor GABRB3 is epigenetically dysregulated in autism brain through altered parental imprinting. As the field of epigenetics of autism is still in its infancy, future studies using higher throughput epigenomic approaches are expected to reveal further epigenetic clues in autistic brain that could be useful for targeted therapies or molecular diagnoses.