Abstract
Many mammalian genes exhibit circadian expression patterns concordant with periodic binding of transcription factors, chromatin modifications, and chromosomal interactions. Here we investigate whether chromatin periodically associates with nuclear lamins. Entrainment of the circadian clock is accompanied, in mouse liver, by a net gain of lamin B1–chromatin interactions genome-wide, after which the majority of lamina-associated domains (LADs) are conserved during the circadian cycle. By tailoring a bioinformatics pipeline designed to identify periodic gene expression patterns, we also observe hundreds of variable lamin B1–chromatin interactions among which oscillations occur at 64 LADs, affecting one or both LAD extremities or entire LADs. Only a small subset of these oscillations however exhibit highly significant 12, 18, 24, or 30 h periodicity. These periodic LADs display oscillation asynchrony between their 5′ and 3′ borders, and are uncoupled from periodic gene expression within or in the vicinity of these LADs. Periodic gene expression is also unrelated to variations in gene-to-nearest LAD distances detected during the circadian cycle. Accordingly, periodic genes, including central clock-control genes, are located megabases away from LADs throughout circadian time, suggesting stable residence in a transcriptionally permissive chromatin environment. We conclude that periodic LADs are not a dominant feature of variable lamin B1–chromatin interactions during the circadian cycle in mouse liver. Our results also suggest that periodic hepatic gene expression is not regulated by rhythmic chromatin associations with the nuclear lamina.
Highlights
Thousands of mammalian genes exhibit autonomous oscillatory patterns of expression concordant with the circadian (24 h) rhythm (Hastings et al, 2018)
We show that periodic lamin B1–chromatin interactions are not a dominant feature of lamina-associated domain (LAD) during the circadian cycle and are uncoupled from periodic gene expression
To entrain the circadian clock, mice were subjected to 24 h fasting and refed ad libitum from circadian time CT0 (Tahara et al, 2011)
Summary
Thousands of mammalian genes exhibit autonomous oscillatory patterns of expression concordant with the circadian (24 h) rhythm (Hastings et al, 2018). In a human colon cancer cell line, a handful of circadian genes have been shown to rhythmically interact with the nuclear lamina, regulating their transcription (Zhao et al, 2015). These observations suggest that nuclear lamins may contribute to the regulation of circadian gene expression. We opted to examine this feature of genome organization in the liver because it is highly responsive to entrainment of the circadian clock at the metabolic level and as such is the most studied organ in investigations of circadian control of transcriptional regulation (Takahashi, 2017) and spatial chromatin conformation (Aguilar-Arnal et al, 2013; Kim et al, 2018). Our data strongly suggest that periodic gene expression is not under direct regulation of rhythmic association of chromatin with the nuclear lamina
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