bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2025–10–12
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham
  1. PBAF/cBAF reorganization on H3.3 chromatin regulates BMAL1 activity in the absence of circadian negative feedback.
  2. Markers of mitochondrial function and oxidative metabolism in skeletal muscle do not display intrinsic circadian regulation in female mice.
  1. Nat Commun. 2025 Oct 09. 16(1): 9000
    PBAF/cBAF reorganization on H3.3 chromatin regulates BMAL1 activity in the absence of circadian negative feedback.
    Dominika Letkova, Aurelie Peticca, Damien Sery, Masahide Seki, Yutaka Suzuki, Kiran Padmanabhan.
      Circadian rhythms in gene expression are coincident with 24 hr dynamics in the recruitment of the core-clock transcription factor heterodimer CLOCK-BMAL1 to chromatin. In the liver, circadian chromatin is characterized by rhythmic histone modifications and the deposition of histone variant H2A.Z. However, other histone variants and remodelers that work in conjunction with CLOCK-BMAL1 on variant chromatin remain poorly understood. Here, we reveal that H3.3 variant histone deposition peaks during the daytime in liver chromatin and that CLOCK-BMAL1 is recruited to H3.3 nucleosomes. Moreover, H3.3:CLOCK-BMAL1 associates with PBAF and BRG1/cBAF complexes - members of the SWI/SNF remodeler family - only during the active phase of the circadian cycle. In clock-disrupted Per1-/-; Per2-/- livers, we observe a depletion in ARID2, the central cog in the molecular assembly of the PBAF complex, accompanied by an increase in H3.3 incorporation. Remarkably, a disassembly of PBAF complex and the concurrent reduction in BRG1 triggers a remodeler reorganization in Per knockout livers, where BRM/cBAF now targets BMAL1 at readily-accessible genomic sites. An abundance of fragile, acetylated H3.3 nucleosomes and a remodeler reorganization provide a mechanistic basis for BMAL1 activity in the absence of PER-mediated negative feedback.
    DOI:  https://doi.org/10.1038/s41467-025-64045-2
  2. Am J Physiol Endocrinol Metab. 2025 Oct 08.
    Markers of mitochondrial function and oxidative metabolism in skeletal muscle do not display intrinsic circadian regulation in female mice.
    Liam S Fitzgerald, Connor Scott Reynoso Spurrier, Nathan Lau, Miles Melamed, Lindsey A Burnett, Gretchen A Meyer, Chang Gui, Andrea L Hevener, James A Sanford, Simon Schenk.
      Mitochondria are key regulators of metabolism and ATP supply in skeletal muscle, while circadian rhythms influence many physiological processes. However, whether mitochondrial function is intrinsically regulated in a circadian manner in mouse skeletal muscle is inadequately understood. Accordingly, we measured post-absorptive transcript abundance of markers of mitochondrial autophagy, dynamics, and metabolism (extensor digitorum longus [EDL], soleus, gastrocnemius), protein abundance of electron transport chain complexes (EDL and soleus), enzymatic activity of SDH (tibialis anterior and plantaris), and maximal mitochondrial respiration (tibialis anterior) in different skeletal muscles from female C57BL/6NJ mice at four zeitgeber times: 1, 7, 13, and 19. Our findings demonstrate that markers of mitochondrial function and oxidative metabolism do not display intrinsic time-of-day regulation at the gene, protein, enzymatic, or functional level. The core-clock genes Bmal1 and Dbp exhibited intrinsic circadian rhythmicity in skeletal muscle (i.e., EDL, soleus, gastrocnemius) and circadian amplitude varied by muscle type. These findings demonstrate that female mouse skeletal muscle does not display circadian regulation of markers of mitochondrial function or oxidative metabolism over 24 hours.
    Keywords:  chronobiology; extensor digitorum longus; soleus; tibialis anterior; time-of-day
    DOI:  https://doi.org/10.1152/ajpendo.00027.2025
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