The other chromatin regulator commonly mutated in cancer is CHD8, which ranks 90th among the genes contributing to tumor suppression in a recent analysis provided by Davoli and colleagues. CHD8 is mutated in about 10% of pancreatic, colorectal, and uterine cancers. In Drosophila, CHD8 is called Kismet, and its deletion leads to the accumulation of H3K27Me3 over the fly genome (108), much in the same way that deletion of BAP or BAF subunits leads to enhanced H3K27Me3 at many loci over the mammalian genome. Another possible mechanism by which CHD8 could contribute to cancer is through binding and inhibition of β-catenin in mammalian cells. CHD8-like Brg and Brm show repeated missense mutations within the ATPase domain, which are likely to have an effect on the protein. Notably, like BAF complexes, CHD8 is implicated in neurologic disease and is the most frequently mutated gene in autism spectrum disorders where loss-of-function mutations in one allele are most common.
