TOC1 (gene)

Last updated
Timing of CAB Expression 1
Identifiers
Organism Arabidopsis thaliana
SymbolAPRR1
Alt. symbolsTOC1, AtTOC1, MFB13.13, PSEUDO-RESPONSE REGULATOR 1
Entrez 836259
RefSeq (mRNA) NM_125531.3
RefSeq (Prot) NP_200946.1
UniProt Q9LKL2
Other data
Chromosome 5: 24.69 - 24.7 Mb
Search for
Structures Swiss-model
Domains InterPro
toc1
Gene
Number of Exons6
Number of Introns5
Size3.49 kb
mRNA
size2713 bp
Protein
Molecular Weight69.2 kDa
pI7.5
Amino Acids618
Location in Arabidopsis
Chromosome5
Distance79.0 cM
Locus TagAT5G61380

Timing of CAB expression 1 is a protein that in Arabidopsis thaliana is encoded by the TOC1 gene. TOC1 is also known as two-component response regulator-like APRR1.

Contents

TOC1 was the first plant gene that, when mutated, yielded a circadian phenotype. It codes for the transcription factor TOC1, which affects the period of plants' circadian rhythms: built-in, malleable oscillations that repeat every 24 hours. The gene codes for a transcriptional repressor, TOC1, one of five pseudo-response regulators (PRR) that mediate the period of the circadian clock in plants. The TOC1 protein is involved in the clock's evening loop, which is a repressilator that directly inhibits transcription of morning loop genes LHY and CCA1. [1] Toc1 gene is expressed in most plant structures and cells, and has its locus on chromosome 5. [2]

Historical context

Discovery

The TOC1 gene was initially discovered by Prof. Andrew Millar and colleagues in 1995 while Millar was a graduate student. Millar developed an innovative forward genetic screen in which he linked a bioluminescent reporter, firefly (luciferase), to expression of CAB (chlorophyll-a,b binding protein—see Light-harvesting complexes of green plants) in Arabidopsis . By measuring bioluminescence over the course of the day, Millar found CAB expression to display oscillatory patterns in constant light and to oscillate with a shorter period in toc1 mutant plants. He also mapped the toc1 gene to chromosome 5. These methods and discoveries were published in and featured on the cover of Science magazine in February 1995. [3]

Partially because the initial studies of clock genes were conducted in Drosophila in the 1970s and then in mammals, it was originally thought that the plant circadian clock functioned similarly to the mammalian clock. In mammals, positive and negative regulatory elements act in feedback loops to drive circadian oscillations; namely, Per and Cry genes are activated by positive elements CLOCK and BMAL to produce proteins that, when phosphorylated, act as negative elements to inhibit the CLOCK:BMAL complex from its activating function. In this way, Per and Cry inhibit their own transcription. [4] [5]

In contrast, Millar's group found the TOC1 protein to be a negative regulator, and the plant clock to be better modeled as a repressilator—a system in which one gene represses another and is in turn repressed by the next, forming an interdependent, oscillating gene network. This finding was achieved through 1) Arabidopsis mutants with constitutive (always turned on) toc1 gene expression, which showed decreased mRNA abundance in both morning loop genes prr7 and 9, cca1, and lhy and evening loop genes gi and elf4; and 2) plants with mutations in toc1 and plants in which RNAi was used to knock out toc1. These mutants with no functional toc1 showed an advanced phase for lhy, suggesting less repression in the absence of TOC1 protein. [6]

A study by Carl Strayer and colleagues found that toc1 gene's transcriptional involvement shortened circadian rhythms in constant dark in addition to constant light, and that TOC1 was circadianly regulated and involved in regulation of its own feedback loop. [7]

Evolutionary History

Homologs of TOC1 have been found in lyrate rockcress, Brassica, papaya, cucumber, strawberry, soybean, lotus, apple, peach, western poplar (populus), castor bean, tomato, potato, grape vine, and chickpea. [8]

21 polymorphisms have been found in Arabidopsis, including substitutions, insertions, and deletions. [2]

Protein characteristics

Structural motifs

Like the other four PRR proteins found in Arabidopsis , TOC1 is located in the nucleus and employs a pseudo-receiver (PR) domain in the N-terminus and a CONSTANS, CONSTANS-LIKE, and TOC1 (CCT) domain at the C-terminus. [1] Through its CCT domain, TOC1 is able to directly bind DNA, and the PR domain is responsible for transcriptional repression activity. [9]

Functions and interactions


TOC1 binds to the G-box and EE-motif promoter regions of genes involved in both the morning and evening transcription-translation feedback loops that drive the plant circadian clock; these genes include PRR7 and 9, CCA1, and LHY in the morning feedback loop and GI and ELF4 in the evening loop. Discrete induction of TOC1 gene expression results in reduced CCA1 and PRR9 expression, indicating that TOC1 plays a repressive rather than stimulatory role in regulating circadian gene expression. [6] Repression of morning loop genes lhy and cca1 was predicted by computational modeling and was the piece of evidence needed to re-define toc1's role in the plant clock as part of a triple negative-component repressilator model rather than a positive/negative-element system of the sort seen in mammals. [10]

The binding pattern of TOC1's CCT domain exhibits circadian oscillations, with maximum binding to G-box and EE motifs—promoter regions that bind transcription factors—occurring at CT15 in the plant's early subjective night. [9] It was shown through the loss of binding rhythms in Arabidopsis mutants with constitutive TOC1 expression that oscillations in TOC1 binding are regulated by the protein's abundance. [6]

TOC1 also appears to be involved in a feedback loop with abscisic acid, a key plant hormone involved in development and stress response. Arabidopsis plants to which varying amounts of ABA were applied showed corresponding differences in TOC1 expression and in circadian period length. Through computational modeling of this feedback loop, TOC1 was shown to be a clock-based influence on patterns of stoma opening and closure, which has traditionally been described as a mainly ABA-regulated process. [11]

Post-translational modifications

Over the circadian cycle, TOC1 is differentially phosphorylated, with peak phosphorylation occurring during the night. [1] In the highly phosphorylated state, TOC1 has a higher binding affinity to the F-box protein ZEITLUPE (ZTL). [1] In addition to controlling TOC1 - ZTL interactions, phosphorylation of the N-terminus of TOC1 protein increases interaction with PRR3, one of the five PRR proteins found in Arabidopsis. [1] From studies with ztl-1 mutants, which have a single missense mutation in the kelch domain of the protein and effectively cause a ztl null mutation, TOC1 protein has been found to be stabilized and TOC1 cycling largely eliminated. [1] While phosphorylation of TOC1 protein stabilizes interactions with ZTL, it also increases TOC1's affinity for PRR3. [1] This ultimately protects TOC1 from ZTL-mediated degradation. [1] PRR3 acts as a competitive inhibitor for the ZTL-TOC1 interaction, as binding of TOC1 to PRR3 results in decreased TOC1 substrate availability for ZTL-dependent degradation. [1] This results in an enhanced amplitude of TOC1 cycling, implying that stable TOC1 cycling is dependent upon ZTL degradation in addition to transcriptional regulation controls. [1]

Agricultural use

To most efficiently use environmental resources such as light, plants generally synchronize their circadian rhythms to match the period of the environment. In a study published in 2005, it was shown that plants whose circadian period matched the period of the light-dark cycle in its environment had increased photosynthesis and growth. [12] Using this knowledge, botanists can take advantage of a mutation in the toc1 gene that has been shown to decrease the period of a plant. It is plausible that these toc1 mutants can easily be used to produce plants in a shorter amount of time, with a smaller amount of energy.

Related Research Articles

<span class="mw-page-title-main">Circadian rhythm</span> Natural internal process that regulates the sleep-wake cycle

A circadian rhythm, or circadian cycle, is a natural oscillation that repeats roughly every 24 hours. Circadian rhythms can refer to any process that originates within an organism and responds to the environment. Circadian rhythms are regulated by a circadian clock whose primary function is to rhythmically co-ordinate biological processes so they occur at the correct time to maximise the fitness of an individual. Circadian rhythms have been widely observed in animals, plants, fungi and cyanobacteria and there is evidence that they evolved independently in each of these kingdoms of life.

A circadian clock, or circadian oscillator, also known as one’s internal alarm clock is a biochemical oscillator that cycles with a stable phase and is synchronized with solar time.

<span class="mw-page-title-main">CLOCK</span> Human protein and coding gene

CLOCK is a gene encoding a basic helix-loop-helix-PAS transcription factor that is known to affect both the persistence and period of circadian rhythms.

The repressilator is a genetic regulatory network consisting of at least one feedback loop with at least three genes, each expressing a protein that represses the next gene in the loop. In biological research, repressilators have been used to build cellular models and understand cell function. There are both artificial and naturally-occurring repressilators. Recently, the naturally-occurring repressilator clock gene circuit in Arabidopsis thaliana and mammalian systems have been studied.

In molecular biology, an oscillating gene is a gene that is expressed in a rhythmic pattern or in periodic cycles. Oscillating genes are usually circadian and can be identified by periodic changes in the state of an organism. Circadian rhythms, controlled by oscillating genes, have a period of approximately 24 hours. For example, plant leaves opening and closing at different times of the day or the sleep-wake schedule of animals can all include circadian rhythms. Other periods are also possible, such as 29.5 days resulting from circalunar rhythms or 12.4 hours resulting from circatidal rhythms. Oscillating genes include both core clock component genes and output genes. A core clock component gene is a gene necessary for to the pacemaker. However, an output oscillating gene, such as the AVP gene, is rhythmic but not necessary to the pacemaker.

Doubletime (DBT), also known as discs overgrown (DCO), is a gene that encodes the double-time protein in fruit flies. Michael Young and his team at Rockefeller University Rockefeller University first identified and characterized the gene in 1998.

<i>KaiC</i> Gene found in cyanobacteria

KaiC is a gene belonging to the KaiABC gene cluster that, together, regulate bacterial circadian rhythms, specifically in cyanobacteria. KaiC encodes for the KaiC protein, which interacts with the KaiA and KaiB proteins in a post-translational oscillator (PTO). The PTO is cyanobacteria master clock that is controlled by sequences of phosphorylation of KaiC protein. Regulation of KaiABC expression and KaiABC phosphorylation is essential for cyanobacteria circadian rhythmicity, and is particularly important for regulating cyanobacteria processes such as nitrogen fixation, photosynthesis, and cell division. Studies have shown similarities to Drosophila, Neurospora, and mammalian clock models in that the kaiABC regulation of the cyanobacteria slave circadian clock is also based on a transcription translation feedback loop (TTFL). KaiC protein has both auto-kinase and auto-phosphatase activity and functions as the circadian regulator in both the PTO and the TTFL. KaiC has been found to not only suppress kaiBC when overexpressed, but also suppress circadian expression of all genes in the cyanobacterial genome.

kaiA is a gene in the "kaiABC" gene cluster that plays a crucial role in the regulation of bacterial circadian rhythms, such as in the cyanobacterium Synechococcus elongatus. For these bacteria, regulation of kaiA expression is critical for circadian rhythm, which determines the twenty-four-hour biological rhythm. In addition, KaiA functions with a negative feedback loop in relation with kaiB and KaiC. The kaiA gene makes KaiA protein that enhances phosphorylation of KaiC while KaiB inhibits activity of KaiA.

White Collar-1 (wc-1) is a gene in Neurospora crassa encoding the protein WC-1. WC-1 has two separate roles in the cell. First, it is the primary photoreceptor for Neurospora and the founding member of the class of principle blue light photoreceptors in all of the fungi. Second, it is necessary for regulating circadian rhythms in FRQ. It is a key component of a circadian molecular pathway that regulates many behavioral activities, including conidiation. WC-1 and WC-2, an interacting partner of WC-1, comprise the White Collar Complex (WCC) that is involved in the Neurospora circadian clock. WCC is a complex of nuclear transcription factor proteins, and contains transcriptional activation domains, PAS domains, and zinc finger DNA-binding domains (GATA). WC-1 and WC-2 heterodimerize through their PAS domains to form the White Collar Complex (WCC).

Circadian Clock Associated 1 (CCA1) is a gene that is central to the circadian oscillator of angiosperms. It was first identified in Arabidopsis thaliana in 1993. CCA1 interacts with LHY and TOC1 to form the core of the oscillator system. CCA1 expression peaks at dawn. Loss of CCA1 function leads to a shortened period in the expression of many other genes.

Steve A. Kay is a British-born chronobiologist who mainly works in the United States. Dr. Kay has pioneered methods to monitor daily gene expression in real time and characterized circadian gene expression in plants, flies and mammals. In 2014, Steve Kay celebrated 25 years of successful chronobiology research at the Kaylab 25 Symposium, joined by over one hundred researchers with whom he had collaborated with or mentored. Dr. Kay, a member of the National Academy of Sciences, U.S.A., briefly served as president of The Scripps Research Institute. and is currently a professor at the University of Southern California. He also served on the Life Sciences jury for the Infosys Prize in 2011.

LUX or Phytoclock1 (PCL1) is a gene that codes for LUX ARRHYTHMO, a protein necessary for circadian rhythms in Arabidopsis thaliana. LUX protein associates with Early Flowering 3 (ELF3) and Early Flowering 4 (ELF4) to form the Evening Complex (EC), a core component of the Arabidopsis repressilator model of the plant circadian clock. The LUX protein functions as a transcription factor that negatively regulates Pseudo-Response Regulator 9 (PRR9), a core gene of the Midday Complex, another component of the Arabidopsis repressilator model. LUX is also associated with circadian control of hypocotyl growth factor genes PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PHYTOCHROME INTERACTING FACTOR 5 (PIF5).

KaiB is a gene located in the highly-conserved kaiABC gene cluster of various cyanobacterial species. Along with KaiA and KaiC, KaiB plays a central role in operation of the cyanobacterial circadian clock. Discovery of the Kai genes marked the first-ever identification of a circadian oscillator in a prokaryotic species. Moreover, characterization of the cyanobacterial clock demonstrated the existence of transcription-independent, post-translational mechanisms of rhythm generation, challenging the universality of the transcription-translation feedback loop model of circadian rhythmicity.

Andrew John McWalter Millar, FRS, FRSE is a Scottish chronobiologist, systems biologist, and molecular geneticist. Millar is a professor at The University of Edinburgh and also serves as its chair of systems biology. Millar is best known for his contributions to plant circadian biology; in the Steve Kay lab, he pioneered the use of luciferase imaging to identify circadian mutants in Arabidopsis. Additionally, Millar's group has implicated the ELF4 gene in circadian control of flowering time in Arabidopsis. Millar was elected to the Royal Society in 2012 and the Royal Society of Edinburgh in 2013.

Pseudo-response regulator (PRR) refers to a group of genes that regulate the circadian oscillator in plants. There are four primary PRR proteins that perform the majority of interactions with other proteins within the circadian oscillator, and another (PRR3) that has limited function. These genes are all paralogs of each other, and all repress the transcription of Circadian Clock Associated 1 (CCA1) and Late Elongated Hypocotyl (LHY) at various times throughout the day. The expression of PRR9, PRR7, PRR5 and TOC1/PRR1 peak around morning, mid-day, afternoon and evening, respectively. As a group, these genes are one part of the three-part repressilator system that governs the biological clock in plants.

The Late Elongated Hypocotyl gene (LHY), is an oscillating gene found in plants that functions as part of their circadian clock. LHY encodes components of mutually regulatory negative feedback loops with Circadian Clock Associated 1 (CCA1) in which overexpression of either results in dampening of both of their expression. This negative feedback loop affects the rhythmicity of multiple outputs creating a daytime protein complex. LHY was one of the first genes identified in the plant clock, along with TOC1 and CCA1. LHY and CCA1 have similar patterns of expression, which is capable of being induced by light. Single loss-of-function mutants in both genes result in seemingly identical phenotypes, but LHY cannot fully rescue the rhythm when CCA1 is absent, indicating that they may only be partially functionally redundant. Under constant light conditions, CCA1 and LHY double loss-of-function mutants fail to maintain rhythms in clock-controlled RNAs.

Transcription-translation feedback loop (TTFL) is a cellular model for explaining circadian rhythms in behavior and physiology. Widely conserved across species, the TTFL is auto-regulatory, in which transcription of clock genes is regulated by their own protein products.

EARLY FLOWERING 3 (ELF3) is a plant-specific gene that encodes the hydroxyproline-rich glycoprotein and is required for the function of the circadian clock. ELF3 is one of the three components that make up the Evening Complex (EC) within the plant circadian clock, in which all three components reach peak gene expression and protein levels at dusk. ELF3 serves as a scaffold to bind EARLY FLOWERING 4 (ELF4) and LUX ARRHYTHMO (LUX), two other components of the EC, and functions to control photoperiod sensitivity in plants. ELF3 also plays an important role in temperature and light input within plants for circadian clock entrainment. Additionally, it plays roles in light and temperature signaling that are independent from its role in the EC.

Elaine Munsey Tobin is a professor of molecular, cell, and developmental biology at the University of California, Los Angeles (UCLA). Tobin is recognized as a Pioneer Member of the American Society of Plant Biologists (ASPB).

Stacey Harmer is a chronobiologist whose work centers on the study of circadian rhythms in plants. Her research focuses on the molecular workings of the plant circadian clock and its influences on plant behaviors and physiology. She is a professor in the Department of Plant Biology at the University of California, Davis.

References

  1. 1 2 3 4 5 6 7 8 9 10 Fujiwara S, Wang L, Han L, Suh SS, Salomé PA, McClung CR, Somers DE (August 2008). "Post-translational regulation of the Arabidopsis circadian clock through selective proteolysis and phosphorylation of pseudo-response regulator proteins". J. Biol. Chem. 283 (34): 23073–83. doi: 10.1074/jbc.M803471200 . PMID   18562312.
  2. 1 2 "Locus: AT5G61380". The Arabidopsis Information Resource. The Ohio State University.
  3. ↑ Millar AJ, Carré IA, Strayer CA, Chua NH, Kay SA (February 1995). "Circadian clock mutants in Arabidopsis identified by luciferase imaging". Science. 267 (5201): 1161–3. Bibcode:1995Sci...267.1161M. doi:10.1126/science.7855595. PMID   7855595. S2CID   1227876.
  4. ↑ Ko CH, Takahashi JS (October 2006). "Molecular components of the mammalian circadian clock". Hum. Mol. Genet. 15 Spec No 2: R271–7. doi: 10.1093/hmg/ddl207 . PMC   3762864 . PMID   16987893.
  5. ↑ Buhr ED, Takahashi JS (2013). "Molecular components of the Mammalian circadian clock". Circadian Clocks. Handbook of Experimental Pharmacology. Vol. 217. pp. 3–27. doi:10.1007/978-3-642-25950-0_1. ISBN   978-3-642-25949-4. PMC   3762864 . PMID   23604473.
  6. 1 2 3 Huang W, Pérez-García P, Pokhilko A, Millar AJ, Antoshechkin I, Riechmann JL, Mas P (April 2012). "Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator" (PDF). Science. 336 (6077): 75–9. Bibcode:2012Sci...336...75H. doi:10.1126/science.1219075. hdl: 10261/47607 . PMID   22403178. S2CID   28750899.
  7. ↑ Strayer C, Oyama T, Schultz TF, Raman R, Somers DE, Más P, Panda S, Kreps JA, Kay SA (August 2000). "Cloning of the Arabidopsis clock gene TOC1, an autoregulatory response regulator homolog". Science. 289 (5480): 768–71. Bibcode:2000Sci...289..768S. doi:10.1126/science.289.5480.768. PMID   10926537. S2CID   46073530.
  8. ↑ "AT5G61380 Locus Search". Plant Genome Duplication Database. University of Georgia.
  9. 1 2 Gendron JM, Pruneda-Paz JL, Doherty CJ, Gross AM, Kang SE, Kay SA (February 2012). "Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor". Proc. Natl. Acad. Sci. U.S.A. 109 (8): 3167–72. Bibcode:2012PNAS..109.3167G. doi: 10.1073/pnas.1200355109 . PMC   3286946 . PMID   22315425.
  10. ↑ Pokhilko A, Fernández AP, Edwards KD, Southern MM, Halliday KJ, Millar AJ (2012). "The clock gene circuit in Arabidopsis includes a repressilator with additional feedback loops". Mol. Syst. Biol. 8: 574. doi:10.1038/msb.2012.6. PMC   3321525 . PMID   22395476.
  11. ↑ Pokhilko A, Mas P, Millar AJ (2013). "Modelling the widespread effects of TOC1 signalling on the plant circadian clock and its outputs". BMC Syst Biol. 7: 23. doi: 10.1186/1752-0509-7-23 . PMC   3614443 . PMID   23506153.
  12. ↑ Dodd AN, Salathia N, Hall A, Kévei E, Tóth R, Nagy F, Hibberd JM, Millar AJ, Webb AA (July 2005). "Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage". Science. 309 (5734): 630–3. Bibcode:2005Sci...309..630D. doi:10.1126/science.1115581. PMID   16040710. S2CID   25739247.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.