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Peer-reviewedCC BY-NC-NDNature communications

Disruption of SWI/SNF ATPases in the mouse liver impairs diurnal gene expression associated with specific promoter features.

  • Nicolaj I Toft1
  • Victor E Goitea1
  • Stine M Præstholm1
  • Catarina M Correia1
  • Isabel Heyde2
  • Majken S Siersbæk1
  • Henrik Oster2
  • Lars Grøntved3
  1. 1Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark.
  2. 2Institute of Neurobiology, Center of Brain, Behavior & Metabolism, University of Lübeck, Lübeck, Germany.
  3. 3Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark. [email protected].
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Abstract

Rhythmic gene expression is controlled by oscillating recruitment of specific transcription factors and co-regulators, including histone-modifying enzymes and chromatin-remodeling complexes. To unravel the significance of SWI/SNF ATPase subunits in diurnal chromatin remodeling, we have mapped diurnal chromatin accessibility, SWI/SNF occupancy, and gene expression throughout a day in the liver of male mice exposed to a night restricted feeding regimen. We find remarkable remodeling during fasting-to-fed transitions, and a third of rhythmic enhancers exhibited diurnal SWI/SNF occupancy and accessibility. Hepatocyte-specific disruption of either of the two mutually exclusive ATPases of SWI/SNF has minor effects on chromatin accessibility. However, simultaneous disruption of both ATPases results in a collapse of chromatin accessibility in the majority of distal cis-regulatory and a third of promoter proximal cis-regulatory elements, which leads to disrupted diurnal gene expression and signs of liver damage and inflammation. SWI/SNF-dependent promoters exhibit similarities with diurnal promoters, indicating a potential sequence-level bias that favors dynamic SWI/SNF-mediated chromatin remodeling. Collectively, this suggests an essential role of SWI/SNF-mediated chromatin remodeling of cis-regulatory regions for rhythmic gene expression and basic liver function.

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Cite

BibTeXRIS
BibTeX
@article{toft2026disruption,
  title = {{Disruption of SWI/SNF ATPases in the mouse liver impairs diurnal gene expression associated with specific promoter features.}},
  author = {Nicolaj I Toft and Victor E Goitea and Stine M Præstholm and Catarina M Correia and Isabel Heyde and Majken S Siersbæk and Henrik Oster and Lars Grøntved},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77798-1},
  url = {https://europepmc.org/article/MED/42901890},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Disruption of SWI/SNF ATPases in the mouse liver impairs diurnal gene expression associated with specific promoter features.
AU  - Nicolaj I Toft
AU  - Victor E Goitea
AU  - Stine M Præstholm
AU  - Catarina M Correia
AU  - Isabel Heyde
AU  - Majken S Siersbæk
AU  - Henrik Oster
AU  - Lars Grøntved
PY  - 2026
DA  - 2026/09/19
JO  - Nature communications
DO  - 10.1038/s41467-026-77798-1
UR  - https://europepmc.org/article/MED/42901890
AB  - Rhythmic gene expression is controlled by oscillating recruitment of specific transcription factors and co-regulators, including histone-modifying enzymes and chromatin-remodeling complexes. To unravel the significance of SWI/SNF ATPase subunits in diurnal chromatin remodeling, we have mapped diurnal chromatin accessibility, SWI/SNF occupancy, and gene expression throughout a day in the liver of male mice exposed to a night restricted feeding regimen. We find remarkable remodeling during fasting-to-fed transitions, and a third of rhythmic enhancers exhibited diurnal SWI/SNF occupancy and accessibility. Hepatocyte-specific disruption of either of the two mutually exclusive ATPases of SWI/SNF has minor effects on chromatin accessibility. However, simultaneous disruption of both ATPases results in a collapse of chromatin accessibility in the majority of distal cis-regulatory and a third of promoter proximal cis-regulatory elements, which leads to disrupted diurnal gene expression and signs of liver damage and inflammation. SWI/SNF-dependent promoters exhibit similarities with diurnal promoters, indicating a potential sequence-level bias that favors dynamic SWI/SNF-mediated chromatin remodeling. Collectively, this suggests an essential role of SWI/SNF-mediated chromatin remodeling of cis-regulatory regions for rhythmic gene expression and basic liver function.
SN  - 2041-1723
ER  -