Skip to main content

Spectrum: Autism Research News

Molecular mechanisms: Gene marker may alter autism brains

by  /  15 April 2014
THIS ARTICLE IS MORE THAN FIVE YEARS OLD

This article is more than five years old. Autism research — and science in general — is constantly evolving, so older articles may contain information or theories that have been reevaluated since their original publication date.

Check marks: The brains of people with autism have elevated levels of an unusual, recently discovered DNA modification called 5-hmC, which helps switch genes on or off.
Julia Yellow

In the brains of people with autism, certain genes are suppressed by a chemical tag that increases binding to MeCP2, the protein implicated in Rett syndrome. The findings were published 21 January in Translational Psychiatry1.

The tag, a hydroxymethyl group bound to the DNA base cytosine and called 5-hmC, is one of several kinds of so-called ‘epigenetic’ modifications, which can turn genes on or off without changing the underlying DNA sequence. These tags can be added or removed in response to environmental influences and help explain why individuals with similar genetic profiles can have different risk levels for conditions such as autism.

A 2012 study suggested that in individuals with autism, hydroxymethylation patterns may contribute to key changes in the cerebellum, a brain region involved in motor control. In the new study, researchers found that MeCP2, a major regulator of gene expression and the protein involved in Rett syndrome, binds to DNA tagged with this group.

MeCP2 regulates a host of genes and is important for learning and memory. Its levels are finely tuned: Disorders result with either too much or too little of the protein. Mutations that lower its levels underlie Rett syndrome, and boys with an extra copy of the MeCP2 gene have autism-like symptoms including developmental delay, seizures and motor deficits.

The new study analyzed MeCP2 binding in the cerebellum in postmortem brains from ten people with autism and ten controls. The team found that MeCP2 binds to genetic regions that regulate two specific genes more frequently than it does in typical brains. Perhaps as a result, the two genes, GAD2 and RELN, are often suppressed in autism2.

The researchers also report that brains from individuals with autism have more 5-hmC tags than controls do. This boosts MeCP2 binding to select genes and regions that control gene expression. The researchers also observed increased levels of an enzyme that adds the hydroxyl groups to methylated DNA.

Because these tags mark genes likely to bind to MeCP2, researchers may be able to use them to index all the genes affected by MeCP2 alterations.

References:

1. Zhubi A. et al. Transl. Psychiatry 4,e349 (2014) PubMed

2. Fatemi S.H. et al. Cerebellum 11, 777-807 (2012) PubMed