Individuals with both rare and common types of autism spectrum disorder share a similar set of epigenetic modifications in the brain, according to a study published in Cell. More than 68% of individuals with different types of autism spectrum disorder show evidence of the same pattern of histone acetylation--a chemical modification of the protein scaffold around which DNA wraps. The findings suggest that a single global epigenetic pattern affecting shared molecular pathways in the brain could underlie diverse manifestations of this psychiatric disease.

Various genetic and environmental factors are known to contribute to ASD. Many studies have focused on structural changes to the genome or DNA sequence variants in protein-coding genes, but these mutations are rare and account for only a small fraction of cases. As a result, scientists have proposed that epigenetic modifications--changes in gene activity that do not affect the DNA sequence--play an important role in ASD. However, many epigenetic studies have focused on a chemical modification of DNA known as methylation, ignoring other important changes that could affect the activity of genes implicated in psychiatric disease.

The researchers focused their analysis on an acetylation mark called H3K27ac because it is implicated in gene activation. They performed an epigenome-wide search for H3K27ac in post-mortem brain tissue samples from the prefrontal cortex, temporal cortex, and cerebellar cortex of individuals with ASD, along with control subjects, aged 10 years and above.

The findings showed that more than 68% of ASD cases shared a common histone acetylation pattern at 5,000 gene loci, despite the wide range of genetic and environmental causes of ASD. By analyzing BrainSpan, an atlas of the developing human brain, they found that gene activation at or near 12 months after birth, which corresponds to the stage of synapse formation and neuronal maturation, was particularly strongly associated with increased acetylation in the ASD brain.

While this study provided an understanding of the molecular changes shared across autism, it stopped short of providing an understanding whether these modifications play a causal role in ASD or are associated with other disease processes and how exactly they contribute to various symptoms. The authors are planning follow-up experiments to test these questions.

Because these epigenomic abnormalities point to specific genes and pathways that are altered in the ASD brain, some of them could turn out to be novel drug targets. Moreover, the study suggests that epigenetic drugs, which are increasingly entering the market as a result of discoveries in the cancer field, could potentially be repurposed for the treatment of ASD.

http://www.cell.com/cell/abstract/S0092-8674(16)31451-9?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867416314519%3Fshowall%3Dtrue