A role in the regulation of transcription by light for RCO-1 and RCM-1, the Neurospora homologs of the yeast Tup1–Ssn6 repressor

Olmedo, María; Navarro‐Sampedro, Laura; Ruger-Herreros, Carmen; Kim, Sang-Rae; Jeong, Byung-Kap; Lee, Bheong-Uk; Corrochano, Luis M.

doi:10.1016/j.fgb.2010.08.001

Cited by 29 publications

(38 citation statements)

References 71 publications

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“…3A, RCM-1 coprecipitated with another protein, which was identified as RCO-1 by mass spectrometry analysis. These results confirm that RCO-1 and RCM-1 form a complex, as previously shown by Sancar et al and as suggested by Olmedo et al (45,46).…”

Section: Resultssupporting

confidence: 92%

“…In the present study, we showed that RCO-1 and RCM-1 function as a complex (45,46) to regulate WC-independent frq transcription and that the PKA KO strains. RCM-1 is localized in the Neurospora nuclei.…”

Section: Discussionsupporting

confidence: 56%

“…We previously showed that RCO-1 regulates the chromatin status at the frq locus, but how RCO-1 acts is not known since RCO-1 was not found to be associated with chromatin at the frq locus (29). The identification of RCM-1 as the partner of RCO-1 (45,46) prompted us to examine whether the complex acts to regulate the chromatin structure at the frq locus via RCM-1. ChIP assays using the RCM-1 antibody showed that RCM-1 is enriched throughout the frq locus with a peak at the C-box of frq promoter (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White Collar-Independent frequency Transcription through Phosphorylation of RCM-1

Liu

et al. 2015

Molecular and Cellular Biology

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Rhythmic activation and repression of clock gene expression is essential for the eukaryotic circadian clock functions. In the Neurospora circadian oscillator, the transcription of the frequency (frq) gene is periodically activated by the White Collar (WC) complex and suppressed by the FRQ-FRH complex. We previously showed that there is WC-independent frq transcription and its repression is required for circadian gene expression. How WC-independent frq transcription is regulated is not known. We show here that elevated protein kinase A (PKA) activity results in WC-independent frq transcription and the loss of clock function. We identified RCM-1 as the protein partner of RCO-1 and an essential component of the clock through its role in suppressing WCindependent frq transcription. RCM-1 is a phosphoprotein and is a substrate of PKA in vivo and in vitro. Mutation of the PKAdependent phosphorylation sites on RCM-1 results in WC-independent transcription of frq and impaired clock function. Furthermore, we showed that RCM-1 is associated with the chromatin at the frq locus, a process that is inhibited by PKA. Together, our results demonstrate that PKA regulates frq transcription by inhibiting RCM-1 activity through RCM-1 phosphorylation. Circadian clocks allow prokaryotic and eukaryotic organisms to regulate their daily molecular, cellular, behavioral, and physiological activities. The eukaryotic circadian clocks are composed of autoregulatory negative-feedback loops, including positive and negative elements that form the core circadian oscillators (1-6). Rhythmic transcriptional activation of the negative elements by the positive elements and rhythmic repression of positive elements by the negative elements are thought to be the main molecular basis for the generation of endogenous rhythmicity in eukaryotic clock systems. In addition to regulation at the transcriptional level, posttranslational modification of clock proteins by phosphorylation plays essential roles in clock functions (7-10).In the filamentous fungus Neurospora crassa, the core circadian negative feedback loop is composed of the positive elements, White Collar 1 (WC-1) and White Collar 2 (WC-2), and the negative elements, FREQUENCY (FRQ) and its partner FRQ-interacting RNA helicase (FRH) (2,3,11,12). WC-1 and WC-2, two Per-Arnt-Sim (PAS) domain-containing transcription factors, form the WC heterodimeric complex that binds to the Clock (C)-box of frq promoter to activate frq transcription (13-18). On the other hand, FRQ and FRH form the FFC complex to inhibit frq transcription by suppressing the activity of the WC complex by promoting WC phosphorylation (19)(20)(21)(22)(23)(24). FRQ is progressively phosphorylated over time before its degradation through the ubiquitin-proteasome pathway mediated by FWD-1 (21, 25-28). Genetic analyses show that the FRQ-dependent phosphorylation of WC-1 and WC-2 that suppresses White Collar complex (WCC) activity is mostly mediated by CKI and CKII (21).WC complex was long thought to be the only transcriptional activator o...

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Section: Resultssupporting

confidence: 92%

Section: Discussionsupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

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Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White Collar-Independent frequency Transcription through Phosphorylation of RCM-1

Liu

et al. 2015

Molecular and Cellular Biology

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“…It will be interesting to determine if TOC1 shares any molecular elements of repression with the earlier-phased PRRs. Recent work in Neurospora crassa reported that orthologs of the S. cerevisiae TUP1-SSN6 complex, RCO1-RCM1 (21,43), play a role in the Neurospora clock by anchoring a repressor complex that globally inhibits morning expression of a suite of circadianregulated metabolic genes with evening phases (44). Expression of the repressor, CONIDIAL SEPARATION 1 (CSP1) is clockcontrolled with a morning phase, and complexes with the corepressor RCO1-RCM1 to place lipid metabolism and membrane composition under circadian regulation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional corepressor TOPLESS complexes with pseudoresponse regulator proteins and histone deacetylases to regulate circadian transcription

Wang

Kim

Somers

2012

Proc. Natl. Acad. Sci. U.S.A.

233

226

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Circadian clocks are ubiquitous molecular time-keeping mechanisms that coordinate physiology and metabolism and provide an adaptive advantage to higher plants. The central oscillator of the plant clock is composed of interlocked feedback loops that involve multiple repressive factors acting throughout the circadian cycle. PSEUDO RESPONSE REGULATORS (PRRs) comprise a five-member family that is essential to the function of the central oscillator. PRR5, PRR7, and PRR9 can bind the promoters of the core clock genes CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) to restrict their expression to near dawn, but the mechanism has been unclear. Here we report that members of the plant Groucho/Tup1 corepressor family, TOPLESS/TOPLESS-RELATED (TPL/TPR), interact with these three PRR proteins at the CCA1 and LHY promoters to repress transcription and alter circadian period. This activity is diminished in the presence of the inhibitor trichostatin A, indicating the requirement of histone deacetylase for full TPL activity. Additionally, a complex of PRR9, TPL, and histone deacetylase 6, can form in vivo, implicating this tripartite association as a central repressor of circadian gene expression. Our findings show that the TPL/TPR corepressor family are components of the central circadian oscillator mechanism and reinforces the role of this family as central to multiple signaling pathways in higher plants.T he circadian clock system consists of multiple interlocked feedback loops that generally contain activating and repressive arms within the loops to sustain robust 24-h oscillations (1-3). Many of the best-characterized elements in the plant circadian system are transcriptional repressors that act during the subjective morning to allow evening expression of their targets, or are expressed during the subjective evening to keep expression of morning genes down at night (4, 5). One well-studied loop of reciprocal repression involves the inhibition of early-day expression of the evening gene TIMING OF CAB EXPRESSION 1 (TOC1; PRR1) by the morning-expressed myb transcription factors CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) (6). TOC1 is the founding member of five closely related PSEUDO RESPONSE REGULATORS (PRRs: PRR9, PRR7, PRR5, PRR3) and binds DNA through a conserved CCT domain at the carboxy terminus, repressing evening expression of both CCA1 and LHY (7, 8). The mechanism of CCA1/LHY-mediated repression of TOC1 requires the corepressor DE-ETIOLATED1 (DET1) to interact with CCA1 and LHY at the TOC1promoter, likely in the context of a larger COP10-DET1-DDB1(CDD) complex (9). TOC1 is also regulated by the related myb-transcription factor, REV8, which binds the TOC1 promoter and likely acts as a positive activator (10, 11). In contrast, the partners and mechanism of lateevening TOC1-mediated repression of CCA1/LHY are unknown. However, a second evening-phased repressor complex, EARLY FLOWERING 3 (ELF3)-EARLY FLOWERING4 (ELF4)-LUX ARRHYTHMO (LUX) has been identified as acting to ...

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“…Our results indicate that this transcription factor could also control glycogen metabolism as a repressor of gsn gene expression in order to favor free glucose inside the cell. Recent results have shown that RCO-1 participates in photoadaptation in N. crassa by repressing gene transcription after a long exposure to light (46), showing that a mutation that affects the conidiation process also presents clock effects (47).…”

Section: Discussionmentioning

confidence: 99%

A Genome-wide Screen for Neurospora crassa Transcription Factors Regulating Glycogen Metabolism

Gonçalves

Cupertino

Freitas

et al. 2011

Molecular & Cellular Proteomics

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Transcription factors play a key role in transcription regulation as they recognize and directly bind to defined sites in promoter regions of target genes, and thus modulate differential expression. The overall process is extremely dynamic, as they have to move through the nucleus and transiently bind to chromatin in order to regulate gene transcription. To identify transcription factors that affect glycogen accumulation in Neurospora crassa, we performed a systematic screen of a deletion strains set generated by the Neurospora Knockout Project and available at the Fungal Genetics Stock Center. In a wild-type strain of N. crassa, glycogen content reaches a maximal level at the end of the exponential growth phase, but upon heat stress the glycogen content rapidly drops. The gene encoding glycogen synthase (gsn) is transcriptionally downregulated when the mycelium is exposed to the same stress condition. We identified 17 deleted strains having glycogen accumulation profiles different from that of the wild-type strain under both normal growth and heat stress conditions. Most of the transcription factors identified were annotated as hypothetical protein, however some of them, such as the PacC, XlnR, and NIT2 proteins, were biochemically well-characterized either in N. crassa or in other fungi. The fungus Neurospora crassa has been widely used as a model organism for the understanding of fundamental aspects of eukaryotic biology. The knowledge of its genome sequence (1) has allowed the identification of proteins required for gene regulation, such as the transcriptional regulatory proteins. An examination of the classes of transcription factors in the N. crassa genome reveals that the organism carries elements shared by simple and complex metazoan models (2). The availability of a set of deletion strains, each carrying a deletion in a specific ORF encoding a transcription factor, allows the screening for genes linked to a particular phenotype. Here we used this mutant strains set to identify transcription factors that either directly or indirectly regulate glycogen metabolism in N. crassa.In many organisms, glycogen is a carbon and energy reserve carbohydrate with an intricate metabolism regulation that senses nutrient availability and other environmental conditions. The amount of glycogen found in a particular situation results from the balance between glycogen synthase and glycogen phosphorylase activities. These enzymes regulate, respectively, the synthesis and degradation of this compound and they are both regulated by phosphorylation. Besides reversible changes in their activities, glycogen levels are also correlated with physiological conditions. In addition, other proteins may also be involved in glycogen accumulation because protein activation resulting from different signaling pathways affects glycogen storage (3,4).In N. crassa, glycogen content reaches a maximal level at the end of the exponential growth phase. However, under stress conditions, such as heat shock, glycogen content drops rapidly (5, 6). The ...

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A role in the regulation of transcription by light for RCO-1 and RCM-1, the Neurospora homologs of the yeast Tup1–Ssn6 repressor

Cited by 29 publications

References 71 publications

Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White Collar-Independent frequency Transcription through Phosphorylation of RCM-1

Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White Collar-Independent frequency Transcription through Phosphorylation of RCM-1

Transcriptional corepressor TOPLESS complexes with pseudoresponse regulator proteins and histone deacetylases to regulate circadian transcription

A Genome-wide Screen for Neurospora crassa Transcription Factors Regulating Glycogen Metabolism

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