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  1. Article ; Online: HNF4A defines tissue-specific circadian rhythms by beaconing BMAL1::CLOCK chromatin binding and shaping the rhythmic chromatin landscape

    Meng Qu / Han Qu / Zhenyu Jia / Steve A. Kay

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Genome-wide occupancy of the master circadian clock transcription factor BMAL1::CLOCK varies across tissues and is reprogrammed in cancers, but how specificity is governed is not known. Here the authors show BMAL1::CLOCK in liver tissue is guided by ... ...

    Abstract Genome-wide occupancy of the master circadian clock transcription factor BMAL1::CLOCK varies across tissues and is reprogrammed in cancers, but how specificity is governed is not known. Here the authors show BMAL1::CLOCK in liver tissue is guided by chromatin accessibility remodeled by HNF4A, shedding new lights onto mechanisms of dysregulated circadian rhythms in hepatocarcinoma.
    Keywords Science ; Q
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Two bHLH transcription factors, bHLH48 and bHLH60, associate with phytochrome interacting factor 7 to regulate hypocotyl elongation in Arabidopsis

    Chuanwei Yang / Sha Huang / Yue Zeng / Chang Liu / Qinyi Ma / Jose Pruneda-Paz / Steve A. Kay / Lin Li

    Cell Reports, Vol 35, Iss 5, Pp 109054- (2021)

    2021  

    Abstract: Summary: The basic helix-loop-helix (bHLH) transcription factor PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) is a central regulator that promotes stem growth by activating growth-related gene expression during shade-avoidance responses. Studying the co- ... ...

    Abstract Summary: The basic helix-loop-helix (bHLH) transcription factor PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) is a central regulator that promotes stem growth by activating growth-related gene expression during shade-avoidance responses. Studying the co-factors of PIF7 can facilitate understanding of the mechanism of PIFs and light signal transduction. Here, we describe the identification of two bHLH transcription factors, bHLH48 and bHLH60 (bHLH48/bHLH60), as essential partners for PIF7-dependent modulation of hypocotyl elongation and function downstream of phytochrome B. These two bHLH factors display DNA binding activity and interact with PIF7. Genetic analysis indicated that bHLH48/bHLH60 and PIF7 are interdependent in promoting hypocotyl elongation. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis identified the substantially overlapping downstream targets of bHLH60 and PIF7. Biochemical analysis revealed that bHLH48/bHLH60 enhance the DNA binding ability of PIF7. These results provide evidence that bHLH48/bHLH60 act as positive partners of PIF7 for mutual benefit in the regulation of hypocotyl elongation.
    Keywords hypocotyl elongation ; bHLH48/bHLH60 ; PIF7 ; DNA binding ability ; transcriptional activity ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Comparative Analysis of Vertebrate Diurnal/Circadian Transcriptomes.

    Greg Boyle / Kerstin Richter / Henry D Priest / David Traver / Todd C Mockler / Jeffrey T Chang / Steve A Kay / Ghislain Breton

    PLoS ONE, Vol 12, Iss 1, p e

    2017  Volume 0169923

    Abstract: From photosynthetic bacteria to mammals, the circadian clock evolved to track diurnal rhythms and enable organisms to anticipate daily recurring changes such as temperature and light. It orchestrates a broad spectrum of physiology such as the sleep/wake ... ...

    Abstract From photosynthetic bacteria to mammals, the circadian clock evolved to track diurnal rhythms and enable organisms to anticipate daily recurring changes such as temperature and light. It orchestrates a broad spectrum of physiology such as the sleep/wake and eating/fasting cycles. While we have made tremendous advances in our understanding of the molecular details of the circadian clock mechanism and how it is synchronized with the environment, we still have rudimentary knowledge regarding its connection to help regulate diurnal physiology. One potential reason is the sheer size of the output network. Diurnal/circadian transcriptomic studies are reporting that around 10% of the expressed genome is rhythmically controlled. Zebrafish is an important model system for the study of the core circadian mechanism in vertebrate. As Zebrafish share more than 70% of its genes with human, it could also be an additional model in addition to rodent for exploring the diurnal/circadian output with potential for translational relevance. Here we performed comparative diurnal/circadian transcriptome analysis with established mouse liver and other tissue datasets. First, by combining liver tissue sampling in a 48h time series, transcription profiling using oligonucleotide arrays and bioinformatics analysis, we profiled rhythmic transcripts and identified 2609 rhythmic genes. The comparative analysis revealed interesting features of the output network regarding number of rhythmic genes, proportion of tissue specific genes and the extent of transcription factor family expression. Undoubtedly, the Zebrafish model system will help identify new vertebrate outputs and their regulators and provides leads for further characterization of the diurnal cis-regulatory network.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Circadian Surprise—It's Not All About Transcription

    Doherty, Colleen J / Steve A. Kay

    Science. 2012 Oct. 19, v. 338, no. 6105

    2012  

    Abstract: The integral role of the circadian clock in numerous aspects of health has prompted extensive study of the molecular architecture of clock networks. Understanding how the clock controls downstream processes has widespread clinical impacts, as it affects ... ...

    Abstract The integral role of the circadian clock in numerous aspects of health has prompted extensive study of the molecular architecture of clock networks. Understanding how the clock controls downstream processes has widespread clinical impacts, as it affects many diseases and biological processes including immune responses, metabolism, and aging (1 – 3). The primary molecular components of the mammalian oscillator and a detailed understanding of the regulatory interactions among them have been well characterized (4 , 5). However, one critical question remains unanswered: How do the cogs of this clock translate the rhythmic regulatory relationship among themselves into the plethora of outputs that are under circadian control? On pages 349 and 379 of this issue, Koike et al. (6) and Morf et al. (7) investigate this problem from opposite ends of the spectrum—a genome-wide discovery approach and the functional characterization of a specific factor, respectively—yet they converge to emphasize the importance of posttranscriptional regulation of messenger RNA (mRNA) levels on the clock.
    Keywords circadian rhythm ; immune response ; mammals ; messenger RNA ; metabolism
    Language English
    Dates of publication 2012-1019
    Size p. 338-340.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1230008
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Identification of pathways that regulate circadian rhythms using a larval zebrafish small molecule screen

    Eric A. Mosser / Cindy N. Chiu / T. Katherine Tamai / Tsuyoshi Hirota / Suna Li / May Hui / Amy Wang / Chanpreet Singh / Andrew Giovanni / Steve A. Kay / David A. Prober

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 14

    Abstract: Abstract The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we ...

    Abstract Abstract The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, and is regulated at both the cellular and organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using a luminescent reporter of molecular circadian rhythms in zebrafish larvae. We identified both known and novel pathways that affect circadian period, amplitude and phase. Several drugs identified in the screen did not affect circadian rhythms in cultured cells derived from luminescent reporter embryos or in established zebrafish and mammalian cell lines, suggesting they act via mechanisms absent in cell culture. Strikingly, using drugs that promote or inhibit inflammation, as well as a mutant that lacks microglia, we found that inflammatory state affects circadian amplitude. These results demonstrate a benefit of performing drug screens using intact animals and provide novel targets for treating circadian rhythm disorders.
    Keywords Medicine ; R ; Science ; Q
    Subject code 571
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Circulating Exosomal miRNAs Signal Circadian Misalignment to Peripheral Metabolic Tissues

    Abdelnaby Khalyfa / Shobhan Gaddameedhi / Elena Crooks / Chunling Zhang / Yan Li / Zhuanhong Qiao / Wojciech Trzepizur / Steve A. Kay / Jorge Andrade / Brieann C. Satterfield / Devon A. Hansen / Leila Kheirandish-Gozal / Hans P. A. Van Dongen / David Gozal

    International Journal of Molecular Sciences, Vol 21, Iss 6396, p

    2020  Volume 6396

    Abstract: Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral oscillators causing metabolic disturbances. A pathway ... ...

    Abstract Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral oscillators causing metabolic disturbances. A pathway conveying such misalignment may involve exosome-based intercellular communication. Fourteen volunteers were assigned to a simulated day shift (DS) or night shift (NS) condition. After 3 days on the simulated shift schedule, blood samples were collected during a 24-h constant routine protocol. Exosomes were isolated from the plasma samples from each of the blood draws. Exosomes were added to naïve differentiated adipocytes, and insulin-induced pAkt/Akt expression changes were assessed. ChIP-Seq analyses for BMAL1 protein, mRNA microarrays and exosomal miRNA arrays combined with bioinformatics and functional effects of agomirs and antagomirs targeting miRNAs in NS and DS exosomal cargo were examined. Human adipocytes treated with exosomes from the NS condition showed altered Akt phosphorylation responses to insulin in comparison to those treated with exosomes from the DS condition. BMAL1 ChIP-Seq of exosome-treated adipocytes showed 42,037 binding sites in the DS condition and 5538 sites in the NS condition, with a large proportion of BMAL1 targets including genes encoding for metabolic regulators. A significant and restricted miRNA exosomal signature emerged after exposure to the NS condition. Among the exosomal miRNAs regulated differentially after 3 days of simulated NS versus DS, proof-of-concept validation of circadian misalignment signaling was demonstrated with hsa-mir-3614-5p. Exosomes from the NS condition markedly altered expression of key genes related to circadian rhythm in several cultured cell types, including adipocytes, myocytes, and hepatocytes, along with significant changes in 29 genes and downstream gene network interactions. Our results indicate that a simulated NS schedule leads to changes in exosomal cargo in the circulation. These changes promote ...
    Keywords Bmal1-dLuc reporter assay ; circadian rhythm ; clock genes ; constant routine ; exosomes ; extracellular vesicles ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 571
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: Circadian rhythms lit up in Chlamydomonas

    Breton, Ghislain / Steve A Kay

    Genome biology. 2006 Feb., v. 7, no. 4

    2006  

    Abstract: Recent work on the circadian clock of the unicellular green alga Chlamydomonas reinhardtii strengthens its standing as a convenient model system for circadian study. It was shown to be amenable to molecular engineering using a luciferase-based real-time ... ...

    Abstract Recent work on the circadian clock of the unicellular green alga Chlamydomonas reinhardtii strengthens its standing as a convenient model system for circadian study. It was shown to be amenable to molecular engineering using a luciferase-based real-time reporter for circadian rhythms. Together with the completed draft genomic sequence, the new system opens the door for genome-scale forward and reverse genetic analysis.
    Keywords Chlamydomonas reinhardtii ; circadian rhythm ; genetic techniques and protocols ; luciferase ; nucleotide sequences ; reporter genes
    Language English
    Dates of publication 2006-02
    Size p. 1201.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/gb-2006-7-4-215
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  8. Article ; Online: CryoEM structures of Arabidopsis DDR complexes involved in RNA-directed DNA methylation

    Somsakul Pop Wongpalee / Shiheng Liu / Javier Gallego-Bartolomé / Alexander Leitner / Ruedi Aebersold / Wanlu Liu / Linda Yen / Maria A. Nohales / Peggy Hsuanyu Kuo / Ajay A. Vashisht / James A. Wohlschlegel / Suhua Feng / Steve A. Kay / Z. Hong Zhou / Steven E. Jacobsen

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: RNA polymerase V transcription in plants, which is needed DNA methylation and transcriptional silencing, requires components of the DDR complex. Here the authors show that all components of the DDR complex co-localize with Pol V and report the cryoEM ... ...

    Abstract RNA polymerase V transcription in plants, which is needed DNA methylation and transcriptional silencing, requires components of the DDR complex. Here the authors show that all components of the DDR complex co-localize with Pol V and report the cryoEM structures of two complexes associated with Pol V recruitment.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: CryoEM structures of Arabidopsis DDR complexes involved in RNA-directed DNA methylation

    Somsakul Pop Wongpalee / Shiheng Liu / Javier Gallego-Bartolomé / Alexander Leitner / Ruedi Aebersold / Wanlu Liu / Linda Yen / Maria A. Nohales / Peggy Hsuanyu Kuo / Ajay A. Vashisht / James A. Wohlschlegel / Suhua Feng / Steve A. Kay / Z. Hong Zhou / Steven E. Jacobsen

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: RNA polymerase V transcription in plants, which is needed DNA methylation and transcriptional silencing, requires components of the DDR complex. Here the authors show that all components of the DDR complex co-localize with Pol V and report the cryoEM ... ...

    Abstract RNA polymerase V transcription in plants, which is needed DNA methylation and transcriptional silencing, requires components of the DDR complex. Here the authors show that all components of the DDR complex co-localize with Pol V and report the cryoEM structures of two complexes associated with Pol V recruitment.
    Keywords Science ; Q
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Daily changes in temperature, not the circadian clock, regulate growth rate in Brachypodium distachyon.

    Dominick A Matos / Benjamin J Cole / Ian P Whitney / Kirk J-M MacKinnon / Steve A Kay / Samuel P Hazen

    PLoS ONE, Vol 9, Iss 6, p e

    2014  Volume 100072

    Abstract: Plant growth is commonly regulated by external cues such as light, temperature, water availability, and internal cues generated by the circadian clock. Changes in the rate of growth within the course of a day have been observed in the leaves, stems, and ... ...

    Abstract Plant growth is commonly regulated by external cues such as light, temperature, water availability, and internal cues generated by the circadian clock. Changes in the rate of growth within the course of a day have been observed in the leaves, stems, and roots of numerous species. However, the relative impact of the circadian clock on the growth of grasses has not been thoroughly characterized. We examined the influence of diurnal temperature and light changes, and that of the circadian clock on leaf length growth patterns in Brachypodium distachyon using high-resolution time-lapse imaging. Pronounced changes in growth rate were observed under combined photocyles and thermocycles or with thermocycles alone. A considerably more rapid growth rate was observed at 28°C than 12°C, irrespective of the presence or absence of light. In spite of clear circadian clock regulated gene expression, plants exhibited no change in growth rate under conditions of constant light and temperature, and little or no effect under photocycles alone. Therefore, temperature appears to be the primary cue influencing observed oscillations in growth rate and not the circadian clock or photoreceptor activity. Furthermore, the size of the leaf meristem and final cell length did not change in response to changes in temperature. Therefore, the nearly five-fold difference in growth rate observed across thermocycles can be attributed to proportionate changes in the rate of cell division and expansion. A better understanding of the growth cues in B. distachyon will further our ability to model metabolism and biomass accumulation in grasses.
    Keywords Medicine ; R ; Science ; Q
    Subject code 580
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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