NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light. We identified three peptidergic cell types that responded to light in the SCN: arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). In each cell type, light-responsive subgroups were enriched for expression of neuronal Per-Arnt-Sim (PAS) domain protein 4 (NPAS4) target genes. Further, mice lacking Npas4 had a longer circadian period under constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN. Our data indicate that NPAS4 is necessary for normal transcriptional responses to light in the SCN and critical for photic phase-shifting of circadian behavior. •Light activates diverse patterns of gene expression in the SCN of the hypothalamus•Light-responsive genes in the SCN show enrichment for NPAS4 regulatory elements•Light-responsive SCN neurons also shown increased expression of NPAS4 target genes•Mice lacking Npas4 have reduced phase shifting to light and longer circadian rhythms In this study, Xu et al. investigate the transcriptional response of the suprachiasmatic nucleus to light. They show that the light-inducible gene Npas4 is involved in mediating the transcriptional response of SCN neurons. Furthermore, loss of Npas4 alters circadian rhythms in mice, suggesting a role of Npas4 in photic entrainment.