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

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. SWI/SNF chromatin remodeling maintains cis-regulatory accessibility in the liver, enabling diurnal gene expression and supporting liver homeostasis during daily fasting-to-feeding transitions.