Fig. 1.

Model for how mutations in chromatin regulator genes cause disease, exemplified by KDM5C mutations. Mutations in chromatin regulator genes affect protein level or activity, such as reduced histone demethylase (HDM) activity of mutant KDM5C. This results in alterations in chromatin conformation at target genes, such as increased H3K4me3 at KDM5C target promoters. Resultant changes in transcription induce cellular phenotypes, to which neurons seem particularly susceptible, leading to disease symptoms.