Cell-Specific Regulation of the Circadian Clock by BMAL1 in the Paraventricular Nucleus: Implications for Regulation of Systemic Biological Rhythms

Authors

Rachel Van Drunen
Yulin Dai
Haichao Wei
Baharan Fekry
Sina Noori
Samay Shivshankar
Rafael Bravo
Zhongming Zhao
Seung-Hee Yoo
Nicholas Justice
Jia Qian Wu
Qingchun Tong
Kristin Eckel-Mahan

Publication Date

7-23-2024

Journal

Cell Reports

Abstract

Circadian rhythms are internal biological rhythms driving temporal tissue-specific, metabolic programs. Loss of the circadian transcription factor BMAL1 in the paraventricular nucleus (PVN) of the hypothalamus reveals its importance in metabolic rhythms, but its functions in individual PVN cells are poorly understood. Here, loss of BMAL1 in the PVN results in arrhythmicity of processes controlling energy balance and alters peripheral diurnal gene expression. BMAL1 chromatin immunoprecipitation sequencing (ChIP-seq) and single-nucleus RNA sequencing (snRNA-seq) reveal its temporal regulation of target genes, including oxytocin (OXT), and restoring circulating OXT peaks in BMAL1-PVN knockout (KO) mice rescues absent activity rhythms. While glutamatergic neurons undergo day/night changes in expression of genes involved in cell morphogenesis, astrocytes and oligodendrocytes show gene expression changes in cytoskeletal organization and oxidative phosphorylation. Collectively, our findings show diurnal gene regulation in neuronal and non-neuronal PVN cells and that BMAL1 contributes to diurnal OXT secretion, which is important for systemic diurnal rhythms.

Keywords

Animals, ARNTL Transcription Factors, Paraventricular Hypothalamic Nucleus, Circadian Clocks, Mice, Mice, Knockout, Neurons, Circadian Rhythm, Oxytocin, Male, Mice, Inbred C57BL, Gene Expression Regulation, Astrocytes, Oligodendroglia

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Associated Data

PMID: 38935503