A working model of a functional role for 5hmC in developmental brain disorder–like behaviors. Control Cntnap2+/− mice (left panel) 5hmC levels (orange lollipops) remain abundant and prevent CLOCK (blue semicircle) from binding to genes implicated in developmental brain disorders (e.g., Gigyf1), which results in adequate gene expression levels (black curved lines) and unaffected behaviors. Cntnap2+/− mice exposed to prenatal stress (PS; lightning bolt; right panel) show a loss of 5hmC abundance in genes implicated in developmental brain disorders (e.g., Gigyf1). This reduction in 5hmC levels allows CLOCK to bind to DNA and repress transcription, which results in developmental brain disorder–like phenotypes.
