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 - Funding Information:
We thank Gokhul Kilaru for bioinformatics support. We thank the University of Texas Southwestern Medical Center Neuroscience Imaging Core Facility and the McDermott Center for Human Growth and Development Next Generation Sequencing Core. We also thank the North Texas Genome Center at the University of Texas at Arlington. This research was supported by grants from the NIH (NS106657 to J.S.T. and NS028829 to M.E.G.), Howard Hughes Medical Institute (to J.S.T.), as well as the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition (Scholar Award 220020467), the Chan Zuckerberg Initiative, an advised fund of the Silicon Valley Community Foundation (HCA-A-1704-01747), and grants from the NIH (DC014702 and MH102603) (to G.K.). P.X. and J.S.T. conceived the study. P.X. and C.J. performed the experiments. P.X. S.B. A.K. B.J. and J.S.T. performed data analyses. M.E.G. G.K. and T.-K.K. provided key resources. J.S.T. T.K.-K. and G.K. supervised the project. P.X. K.H.C. and J.S.T. wrote the manuscript. All authors were involved in reviewing and editing. The authors declare no competing interests. We worked to ensure sex balance in the selection of non-human subjects. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. The author list of this paper includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
Funding Information:
We thank Gokhul Kilaru for bioinformatics support. We thank the University of Texas Southwestern Medical Center Neuroscience Imaging Core Facility and the McDermott Center for Human Growth and Development Next Generation Sequencing Core. We also thank the North Texas Genome Center at the University of Texas at Arlington. This research was supported by grants from the NIH ( NS106657 to J.S.T. and NS028829 to M.E.G.), Howard Hughes Medical Institute (to J.S.T.), as well as the James S. McDonnell Foundation 21st Century Science Initiative in Understanding Human Cognition (Scholar Award 220020467 ), the Chan Zuckerberg Initiative , an advised fund of the Silicon Valley Community Foundation ( HCA-A-1704-01747 ), and grants from the NIH ( DC014702 and MH102603 ) (to G.K.).
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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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 -