Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis

Abstract

The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

Figure 1.

Phosphorylation Modulates TOC1 Protein Stability. Phosphorylation of TOC1 enhances the interaction with ZTL, which leads to proteasomal degradation. ZTL also targets PRR5 for degradation. Phosphorylation also favors TOC1 stabilization both by PRR3-mediated competitive inhibition of the proteasomal degradation and by PRR5 nuclear sequestration. ZTL is stabilized by interaction with GI and HSP90. GI is regulated by the COP1-ELF3 complex. P, phosphorylation; Ub, ubiquitination.

Figure 2.

Epigenetic Regulation at the Core of the Arabidopsis Circadian Oscillator. H3K56ac, H3K9/14ac, H3K4me3, and H3K4me2 are representative oscillating epigenetic marks that correlate with and contribute to the rhythmic expression of the core clock genes. The timing of histone acetylation regulates gene expression by influencing transcription factor accessibility, whereas histone trimethylation antagonizes clock repressor binding. The molecular components responsible for the reversible histone acetylation and demethylation are not known. SDG2/ATXR3 is responsible for histone trimethylation at the core of the Arabidopsis circadian clock. HMT, histone methyltransferase; HDM, histone demethylase.