Rhythmic feeding contributed to gene expression rhythms, but with lower amplitudes compared to the circadian clock.
Differences in gene expression levels observed between wild-type and knockout mice were associated with .
In PARbZip knockout mice, mean expression levels of PARbZip target genes were more affected than their rhythmic patterns.
Identified genes that lost rhythmicity in PARbZip knockouts were found to be indirect targets.
Simplified
The and feeding rhythms are both important regulators of in the liver. To further dissect the respective contributions of feeding and the clock, we analyzed differential rhythmicity of liver tissue samples across several conditions. We developed a statistical method tailored to compare rhythmic liver messenger RNA (mRNA) expression in mouse knockout models of multiple clock genes, as well as PARbZip output transcription factors (//). Mice were exposed to ad libitum or night-restricted feeding under regular light-dark cycles. During ad libitum feeding, genetic ablation of the core clock attenuated rhythmic-feeding patterns, which could be restored by the night-restricted feeding regimen. High-amplitude mRNA expression rhythms in wild-type livers were driven by the circadian clock, but rhythmic feeding also contributed to rhythmic gene expression, albeit with significantly lower amplitudes. We observed thatand/knockouts differed in their residual rhythmic gene expression. Differences in mean expression levels between wild types and knockouts correlated with rhythmic gene expression in wild type. Surprisingly, in PARbZip knockout mice, the mean expression levels of PARbZip targets were more strongly impacted than their rhythms, potentially due to the rhythmic activity of the D-box-repressor NFIL3. Genes that lost rhythmicity in PARbZip knockouts were identified to be indirect targets. Our findings provide insights into the diurnal transcriptome in mouse liver as we identified the differential contributions of several core clock regulators. In addition, we gained more insights on the specific effects of the feeding-fasting cycle. Hlf Dbp Tef Bmal1Cry1 2
Key numbers
33%
System-Driven Genes
Percentage of rhythmic genes in wild-type mice that are system-driven.
54%
Loss of Rhythmicity
Percentage of rhythmic transcripts that lost rhythmicity in clock-disrupted mice.
32%
Restoration of Rhythmicity
Percentage of rhythmic genes restored under night-restricted feeding in clock-disrupted mice.
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