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. INTRODUCTIONThe circadian clock is a cellular time-keeper mechanism able to perceive external synchronizing inputs to generate endogenous rhythmic outputs with a period of ;24 h. In many plant species, synchronization of the clock with the environment confers fitness advantages by controlling key essential processes, such as photosynthetic activity, hypocotyl elongation, and the floral transition (Doyle et al., 2002;Green et al., 2002;Imaizumi et al., 2003;Dodd et al., 2005;Zhang et al., 2008;Niwa et al., 2009;Resco et al., 2009;Yerushalmi and Green, 2009;Nusinow et al., 2011). A large fraction of the plant transcriptome is clock controlled, suggesting that the circadian clock globally modulates diverse signals and metabolic pathways that mediate development and environmental adaptation responses (Nagel and Kay, 2012).The transcriptional regulation of several clock components has been well characterized at a molecular level over the past years (reviewed in Carré and Veflingstad, 2013). Multiple intertwined regulatory networks define the basic architecture of the Arabidopsis thaliana circadian clock. Two single MYB transcription factors, CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) (Schaffer et al., 1998), and TIMING OF CAB EXPRESSION1/ PSEUDO-RESPONSE REGULATOR1 (TOC1/PRR1) (Strayer et al., 2000;Makino et al., 2002) comprise a central regulatory module (Alabadí et al., 2001). CCA1 and LHY repress TOC1 expression that in turn represses the transcription of CCA1 and LHY (Gendron et al., 2012;Huang et al., 2012). This regulatory module is interlocked with a morning loop and an evening loop (Locke et al., 2006). In the morning loop, members of the PRR family (PRR5, PRR7, and PRR9) bind to promoters of CCA1 and LHY ...

Epigenetic Basis of Morphological Variation and Phenotypic Plasticity inArabidopsis thaliana

“…As to the nature of these pleiotropic loci, we can only speculate that these are transcription factor genes or genes involved in metabolism or circadian rhythms. It is well known that transcription factors, metabolism, and clock genes can be under epigenetic regulation (Manning et al, 2006; Alvarez-Venegas , 2007;Cazzonelli et al, 2009;Quadrana et al, 2014;Seo and Mas, 2014). Alternatively, trans-acting RNAs produced from differentially methylated TEs might affect multiple targets in the genome, causing pleiotropic effects.…”

Quantitative Circadian Phosphoproteomic Analysis of Arabidopsis Reveals Extensive Clock Control of Key Components in Physiological, Metabolic, and Signaling Pathways

“…In plants, TIMING OF CAB EXPRESSION1 (TOC1) 1 and other pseudo-response regulator (PRR) proteins are differentially phosphorylated over the course of the circadian cycle (16) and both CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) are phosphorylated by casein kinase 2 (CK2) (17,18). In some cases the significance is known (16,19,20). For example, TOC1 phosphorylation enhances dimerization with PRR3 and binding to ZEITLUPE (ZTL), the F-box protein that mediates TOC1 ubiquitination (16,21).…”

Time-dependent sequestration of RVE8 by LNK proteins shapes the diurnal oscillation of anthocyanin biosynthesis

“…TOC1 in turn represses CCA1 and LHY (8, 9) as well as the other members of the PRR family (PRR9, 7, and 5) (10) that in turn act as repressors of CCA1 and LHY expression (11). TOC1 also represses LUX ARRHYTHMO (LUX) and EARLY FLOWERING 4 (ELF4) (9), whose protein products interact with EARLY FLOWERING 3 (ELF3) to form the socalled Evening Complex (EC) (12).Chromatin changes at the promoters of the core oscillator genes also play an important role modulating clock gene expression and function (13,14). The single Myb-like transcription factor REVEILLE8/LHY-CCA1-LIKE5 (RVE8/LCL5) (15) antagonizes CCA1 repressing function in the regulation of Histone3 acetylation at TOC1 promoter (16).…”

“…Chromatin changes at the promoters of the core oscillator genes also play an important role modulating clock gene expression and function (13,14). The single Myb-like transcription factor REVEILLE8/LHY-CCA1-LIKE5 (RVE8/LCL5) (15) antagonizes CCA1 repressing function in the regulation of Histone3 acetylation at TOC1 promoter (16).…”