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Proceedings of the National Academy of... Jun 2019The circadian clock provides organisms with the ability to adapt to daily and seasonal cycles. Eukaryotic clocks mostly rely on lineage-specific...
The circadian clock provides organisms with the ability to adapt to daily and seasonal cycles. Eukaryotic clocks mostly rely on lineage-specific transcriptional-translational feedback loops (TTFLs). Posttranslational modifications are also crucial for clock functions in fungi and animals, but the posttranslational modifications that affect the plant clock are less understood. Here, using chemical biology strategies, we show that the CASEIN KINASE 1 LIKE (CKL) family is involved in posttranslational modification in the plant clock. Chemical screening demonstrated that an animal CDC7/CDK9 inhibitor, PHA767491, lengthens the circadian period. Affinity proteomics using a chemical probe revealed that PHA767491 binds to and inhibits multiple CKL proteins, rather than CDC7/CDK9 homologs. Simultaneous knockdown of CKL-encoding genes lengthened the circadian period. CKL4 phosphorylated transcriptional repressors PSEUDO-RESPONSE REGULATOR 5 (PRR5) and TIMING OF CAB EXPRESSION 1 (TOC1) in the TTFL. PHA767491 treatment resulted in accumulation of PRR5 and TOC1, accompanied by decreasing expression of PRR5- and TOC1-target genes. A double mutant was hyposensitive to PHA767491-induced period lengthening. Together, our results reveal posttranslational modification of transcriptional repressors in plant clock TTFL by CK1 family proteins, which also modulate nonplant circadian clocks.
Topics: Arabidopsis; Arabidopsis Proteins; Casein Kinase I; Circadian Clocks; Circadian Rhythm; Gene Expression Regulation, Plant; Phosphorylation; Protein Processing, Post-Translational; Transcription Factors; Transcription, Genetic
PubMed: 31097584
DOI: 10.1073/pnas.1903357116 -
Breeding Science Mar 2019Flowering time control in plants is a major limiting factor on the range of species. Day length, perceived via the photoperiodic pathway, is a critical factor for the...
Flowering time control in plants is a major limiting factor on the range of species. Day length, perceived via the photoperiodic pathway, is a critical factor for the induction of flowering. The module of -- in the long day (LD) plant is conserved in diverse plant species including the short day (SD) plant rice, where this module comprises ()-. , the rice ortholog of , has dual functions in the regulation of flowering time, promoting flowering in SD conditions and delaying it in LD conditions. We herein show genetic interactions among three LD repressor genes: , , (), and (). Genetic analyses, including segregation analyses, evaluations of near isogenic lines, and transformation for flowering time demonstrated that promoted flowering time in inductive SD and non-inductive LD conditions in genetic condition of loss-of-function and () in rice. Functional or may switch the genetic effects of from the promotion to the delay of flowering times in LD conditions.
PubMed: 31086490
DOI: 10.1270/jsbbs.18060 -
Frontiers in Plant Science 2019The circadian clock synchronizes endogenous rhythmic processes with environmental cycles and maximizes plant fitness. Multiple regulatory layers shape circadian...
The circadian clock synchronizes endogenous rhythmic processes with environmental cycles and maximizes plant fitness. Multiple regulatory layers shape circadian oscillation, and chromatin modification is emerging as an important scheme for precise circadian waveforms. Here, we report the role of an evolutionarily conserved Sin3-histone deacetylase complex (HDAC) in circadian oscillation in . () and , which are key components of Sin3-HDAC complex, are circadianly-regulated and possibly facilitate the temporal formation of the Sin3-HDAC complex at dusk. The evening-expressed AFR proteins bind directly to the () and () promoters and catalyze histone 3 (H3) deacetylation at the cognate regions to repress expression, allowing the declining phase of their expression at dusk. In support, the and genes were de-repressed around dusk in the double mutant. These findings indicate that periodic histone deacetylation at the morning genes by the Sin3-HDAC complex contributes to robust circadian maintenance in higher plants.
PubMed: 30833956
DOI: 10.3389/fpls.2019.00171 -
Scientific Reports Feb 2019Circadian clocks regulate the daily timing of metabolic, physiological, and behavioral activities to adapt organisms to day-night cycles. In the model plant Arabidopsis...
Circadian clocks regulate the daily timing of metabolic, physiological, and behavioral activities to adapt organisms to day-night cycles. In the model plant Arabidopsis thaliana, transcript-translational feedback loops (TTFL) constitute the circadian clock, which is conserved among flowering plants. Arabidopsis TTFL directly regulates key genes in the clock-output pathways, whereas the pathways for clock-output control in other plants is largely unknown. Here, we propose that the transcriptional networks of clock-associated pseudo-response regulators (PRRs) are conserved among flowering plants. Most PRR genes from Arabidopsis, poplar, and rice encode potential transcriptional repressors. The PRR5-target-like gene group includes genes that encode key transcription factors for flowering time regulation, cell elongation, and chloroplast gene expression. The 5'-upstream regions of PRR5-target-like genes from poplar and rice tend to contain G-box-like elements that are potentially recognized by PRRs in vivo as has been shown in Arabidopsis. Expression of PRR5-target-like genes from poplar and rice tends to decrease when PRRs are expressed, possibly suggesting that the transcriptional network of PRRs is evolutionarily conserved in these plants.
Topics: Arabidopsis; Arabidopsis Proteins; Circadian Clocks; Circadian Rhythm; Gene Expression Regulation, Plant; Gene Regulatory Networks; Magnoliopsida; Oryza; Populus; Promoter Regions, Genetic; Repressor Proteins; Transcription Factors
PubMed: 30814643
DOI: 10.1038/s41598-019-39720-2 -
PeerJ 2019Genes encoding pseudo-response regulator (PRR) proteins play significant roles in plant circadian clocks. In this study, four genes related to flowering time were...
Genes encoding pseudo-response regulator (PRR) proteins play significant roles in plant circadian clocks. In this study, four genes related to flowering time were isolated from . Phylogenetic analysis showed that they are highly homologous to the counterparts of PRRs of and named as , , , and . Conserved motifs prediction indicated that most of the closely related members in the phylogenetic tree share common protein sequence motifs, suggesting functional similarities among the PRR proteins within the same subtree. In order to explore functions of the genes, we selected two varieties for comparison; that is, a short-day sensitive Zijiao and a short-day insensitive Aoyunbaixue. Compared to Aoyunbaixue, Zijiao needs 13 more days to complete the flower bud differentiation. Evidence from spatio-temporal gene expression patterns demonstrated that the are highly expressed in flower and stem tissues, with a growing trend across the developmental process. In addition, we also characterized the expression patterns and found that can maintain their circadian oscillation features to some extent under different photoperiod treatment conditions. These lines of evidence indicated that the four undergo circadian oscillation and possibly play roles in regulating the flowering time of .
PubMed: 30809439
DOI: 10.7717/peerj.6420 -
CNS Oncology Mar 2019
Review
Topics: Central Nervous System Neoplasms; Clinical Trials as Topic; Humans; Practice Patterns, Physicians'; Treatment Outcome
PubMed: 30806082
DOI: 10.2217/cns-2018-0007 -
Frontiers in Plant Science 2019The circadian system ensures that plants respond appropriately to environmental change by predicting regular transitions that occur during diel cycles. In order to be...
The circadian system ensures that plants respond appropriately to environmental change by predicting regular transitions that occur during diel cycles. In order to be most useful, the circadian system needs to be compensated against daily and seasonal changes in temperature that would otherwise alter the pace of this biological oscillator. We demonstrate that an evening-phased protein, the putative histone demethylase JMJD5, contributes to temperature compensation. is co-expressed with components of the Evening Complex, an agglomeration of proteins including EARLY FLOWERING3 (ELF3), ELF4, and LUX ARRHYTHYMO (LUX), which also integrates temperature changes into the molecular clockwork. One role of the Evening Complex is to regulate expression of () and , important components of the temperature compensation mechanism. Surprisingly we find that LUX, but not other Evening Complex components, is dispensable for clock function at low temperatures. Further genetic analysis suggests JMJD5 acts in a parallel pathway to LUX within the circadian system. Although an intact JMJD5 catalytic domain is required for its function within the clock, our findings suggest JMJD5 does not directly regulate H3K36 methylation at circadian loci. Such data refine our understanding of how JMDJ5 acts within the Arabidopsis circadian system.
PubMed: 30774641
DOI: 10.3389/fpls.2019.00057 -
Contrast Media & Molecular Imaging 2018Glioblastoma (GBM) is the most common primary malignant type of brain neoplasm in adults and carries a dismal prognosis. The current standard of care for GBM is surgical... (Review)
Review
Glioblastoma (GBM) is the most common primary malignant type of brain neoplasm in adults and carries a dismal prognosis. The current standard of care for GBM is surgical excision followed by radiation therapy (RT) with concurrent and adjuvant temozolomide-based chemotherapy (TMZ) by six additional cycles. In addition, antiangiogenic therapy with an antivascular endothelial growth factor (VEGF) agent has been used for recurrent glioblastoma. Over the last years, new posttreatment entities such as pseudoprogression and pseudoresponse have been recognized, apart from radiation necrosis. This review article focuses on the role of different imaging techniques such as conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), dynamic contrast enhancement (DCE-MRI) and dynamic susceptibility contrast (DSE-MRI) perfusion, magnetic resonance spectroscopy (MRS), and PET/SPECT in differentiation of such treatment-related changes from tumor recurrence.
Topics: Diagnostic Imaging; Disease Progression; Glioblastoma; Glioma; Humans; Neoplasm Recurrence, Local
PubMed: 30627060
DOI: 10.1155/2018/6828396 -
Journal of Magnetic Resonance Imaging :... Jan 2019Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but... (Review)
Review
Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but unable to differentiate tumor progression from treatment-related effects. Pseudoprogression appears as new enhancement, and thus mimics tumor progression on conventional MRI. Contrarily, a decrease in enhancement or edema on conventional MRI during antiangiogenic treatment can be due to pseudoresponse and is not necessarily reflective of a favorable outcome. Neovascularization is a hallmark of tumor progression but not for posttherapeutic effects. Perfusion-weighted MRI provides a plethora of additional parameters that can help to identify this neovascularization. This review shows that perfusion MRI aids to identify tumor progression, pseudoprogression, and pseudoresponse. The review provides an overview of the most applicable perfusion MRI methods and their limitations. Finally, future developments and remaining challenges of perfusion MRI in treatment evaluation in neuro-oncology are discussed. Level of Evidence: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:11-22.
Topics: Brain; Brain Neoplasms; Contrast Media; Disease Progression; Edema; Glioblastoma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Neuroimaging; Reproducibility of Results
PubMed: 30561164
DOI: 10.1002/jmri.26306 -
Bioengineering (Basel, Switzerland) Nov 2018Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis,... (Review)
Review
Imaging plays a critical role in the management of the highly complex and widely diverse central nervous system (CNS) malignancies in providing an accurate diagnosis, treatment planning, response assessment, prognosis, and surveillance. Contrast-enhanced magnetic resonance imaging (MRI) is the primary modality for CNS disease management due to its high contrast resolution, reasonable spatial resolution, and relatively low cost and risk. However, defining tumor response to radiation treatment and chemotherapy by contrast-enhanced MRI is often difficult due to various factors that can influence contrast agent distribution and perfusion, such as edema, necrosis, vascular alterations, and inflammation, leading to pseudoprogression and pseudoresponse assessments. Amino acid positron emission tomography (PET) is emerging as the method of resolving such equivocal lesion interpretations. Amino acid radiotracers can more specifically differentiate true tumor boundaries from equivocal lesions based on their specific and active uptake by the highly metabolic cellular component of CNS tumors. These therapy-induced metabolic changes detected by amino acid PET facilitate early treatment response assessments. Integrating amino acid PET in the management of CNS malignancies to complement MRI will significantly improve early therapy response assessment, treatment planning, and clinical trial design.
PubMed: 30487391
DOI: 10.3390/bioengineering5040104