Autism spectrum disorders (ASD) are mostly seen as a range of mental conditions, so researchers from the University of Massachusetts Medical School focused in on the prefrontal cortex (PFC) neurons of autistic individuals, and mapped their H3K4me3 epigenomes in order to better understand the complex condition.
The project compared autistic PFC neuron profiles to a panel of controls ranging in age from 1 to 70 years. The UMass team ran ChIP-seq profiling experiments with an H3K4me3 antibody to create genome-wide maps of the H3K4me3 mark in NeuN nuclei from the PFCs of 16 ASD subjects, and control samples. After all the sequencing analysis was finished, here’s what they saw:
- Autistic patients weren’t globally different in H3K4me3 occupancy, showing similar marks at known promoters, and an age-appropriate promoter H3K4me3 profile.
- However, neuronal chromatin in some autism cases had excessive spreading of H3K4me3 marks into nucleosomes farther away from the TSS.
- A closer look at H3K4me3 loci found that 503 (autism-up) were increased and 208 (autism-down) loci were decreased in a subset of autistic subjects. And of those, 330 autism-up loci and 139 autism-down loci overlapped with promoters.
The authors believe that this study is the first to attempt to explore the chromatin structures of PFC neurons from ASD subjects. The scientists conclude that certain autistic individuals are affected by a loss or excess of H3K4me3 at hundreds of loci, leading to aberrant transcript expression and traits associated with ASD. Of course, the changes are highly variable between patients and indicate very complex interactions between the genetic and epigenetic mechanisms affecting autism spectrum disorders. It’s clear that even more study will be needed to grasp the biological meaning of this new data.
Wrap your mind around the full article in Archives of General Psychiatry, November 2011.