In the nucleus, DNA wraps around proteins to form a structure known as chromatin, and epigenetic modifications to either the proteins or the DNA can determine whether the chromatin hides or exposes a gene for RNA production. Chromatin modifications can have a wide-ranging impact on which genes are expressed, even without a mutation in the DNA sequence. Beaudet and his colleagues are looking for unusual patterns of chromatin modifications associated with autism, using techniques that uncover these marks on the proteins and DNA recovered from the nuclei of neurons. From the postmortem brain tissue from people with autism, the team plans to isolate chromatin and use antibodies to detect particular histone modifications known to affect gene expression. The researchers will also sequence the isolated DNA, looking for both mutations and methylation marks. This combined strategy allows screening of the chromatin in the neuron nuclei across the entire genome. The researchers will also analyze autism-associated genomic regions with even higher resolution to detect any epigenetic changes that would not be detected by traditional sequencing. In a complementary set of experiments, the investigators are carefully assaying the neurons' RNA profiles to determine which genes are up- or down-regulated in autism, which may point to new genes or pathways.