Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System

Abstract

A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally-testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology.

Feedback Loops of the Mammalian Circadian Clock Constitute Repressilator

“…A repressilator was also suggested for the plant circadian clock [10, 57] supporting—despite the difference of the mammalian and plant clock—the hypothesis that a rhythmic gene regulatory network using a repressilator motif can generate circadian rhythms.…”

Protein sequestration versus Hill‐type repression in circadian clock models

“…In particular, in plants, the core transcriptional NFL consists of series of transcriptional repressions, which has a similar design as the repressilator or quadripressilator [5,[171][172][173]. While the detailed transcriptional repression mechanism has not been fully identified, currently models have assumed Hill-type repression [171,[174][175][176][177]. Further research should be undertaken to investigate which type of transcriptional repression mechanism is most appropriate for plant circadian clock models.…”

ELONGATED HYPOCOTYL 5 mediates blue light signalling to the Arabidopsis circadian clock

“…Eukaryotic circadian oscillators are built on transcriptional/translational negative feedback loops that are operated by mutual interactions among the so‐called clock genes and the corresponding clock proteins. The structure of the plant clock is highly complicated and relies on four interconnected regulatory loops (Foo et al ., ). Recent reviews provide detailed descriptions of the oscillator (Hsu and Harmer, ; Greenham and McClung, ).…”