Rhythmic chromatin interactions with lamin B1 reflect stochasticity in variable lamina-associated domains during the circadian cycle

Abstract

Many mammalian genes exhibit circadian expression patterns concordant with periodic binding of transcription factors, chromatin modifications and chromosomal interactions. Here, we report periodic interactions of chromatin with nuclear lamins, suggesting rhythmic associations with the nuclear lamina.Entrainment of the circadian clock is accompanied in mouse liver by a gain of lamin B1-chromatin interactions, followed by oscillations in these interactions at hundreds of lamina-associated domains (LADs). A subset of these oscillations exhibit distinct 12, 18, 24 or 30-h periodicity in our dataset, and affect one or both LAD borders or entire stand-alone LADs. However, most LADs are conserved during the circadian cycle, and periodic LADs are seldom occurrences rather than dominant features of variable LADs. Periodic LADs display oscillation asynchrony between 5' and 3' LAD borders, and are uncoupled from periodic gene expression within or in vicinity of these LADs. Accordingly, periodic genes, including central clock-control genes, are often located megabases away from LADs, suggesting residence in a transcriptionally permissive environment throughout the circadian cycle. Autonomous oscillatory associations of the genome with nuclear lamins provide new evidence for rhythmic spatial chromatin configurations. Nevertheless, our data suggest that periodic LADs reflect stochasticity in lamin-chromatin interactions underlying chromatin dynamics in the liver during the circadian cycle. They also argue that periodic gene expression is by and large not regulated by rhythmic chromatin associations with the nuclear lamina.

Nuclear Lamin B1 Interactions With Chromatin During the Circadian Cycle Are Uncoupled From Periodic Gene Expression

“…), the Research Council of Norway and South-East Health Norway. An earlier version of this manuscript has been released as a pre-print at: bioRxiv 584011; doi: (Brunet et al, 2019).…”