TY - JOUR
T1 - NPAS4 regulates the transcriptional response of the suprachiasmatic nucleus to light and circadian behavior
AU - Xu, Pin
AU - Berto, Stefano
AU - Kulkarni, Ashwinikumar
AU - Jeong, Byeongha
AU - Joseph, Chryshanthi
AU - Cox, Kimberly H.
AU - Greenberg, Michael E.
AU - Kim, Tae Kyung
AU - Konopka, Genevieve
AU - Takahashi, Joseph S.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/10/20
Y1 - 2021/10/20
N2 - 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.
AB - 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.
KW - NPAS4
KW - light simulation
KW - single-nucleus RNA sequencing
KW - suprachiasmatic nucleus
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UR - http://www.scopus.com/inward/citedby.url?scp=85117167940&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2021.07.026
DO - 10.1016/j.neuron.2021.07.026
M3 - Article
C2 - 34416169
AN - SCOPUS:85117167940
SN - 0896-6273
VL - 109
SP - 3268-3282.e6
JO - Neuron
JF - Neuron
IS - 20
ER -