Deletion of autism risk factor Chd8 in postmitotic neurons affects activity-dependent transcriptional responses. Mus musculus

The gene encoding chromodomain helicase DNA-binding protein 8 (CHD8) is identified as one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Whereas CHD8 serves as a key transcriptional regulator by chromatin remodeling thereby controls proliferation and differentiation of neural progenitor cells, CHD8 function in postmitotic neuron and adult brain has remained unclear. Here we show that Chd8 ablation in postmitotic neuron reduces the expression of neuronal genes. CHD8 regulates the expression of activity-dependent genes induced by neuronal activity. Furthermore, we generated mice with CHD8 deficiency in adult brain and found that activity-dependent transcriptional responses after kainic acid-induced seizure are attenuated by CHD8 depletion in the hippocampus. Our findings suggest the functional importance of CHD8 in postmitotic neuron and adult brain, which may contribute to in some forms of ASD pathogenesis by CHD8 haploinsufficiency.