DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition

Xiao, Ling; Dang, Yunkun; Matsuura, Toru; He, Yubo; He, Qun; Hong, Christian I.; Liu, Yi

doi:10.1016/j.molcel.2017.05.029

Cited by 24 publications

(29 citation statements)

References 75 publications

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“…We successfully obtained one mutant I349ΔH2A.Z (verified by both PCR and southern blot, S3 Fig), suggesting that the deletion of H2A.Z in F. graminearum is non-lethal. This result is consistent with previous experiments in fungi that found H2A.Z as non-essential in N. crassa [64], S. cerevisiae [36], or Schizosaccharomyces pombe [65] for example, although they exhibited reduced growth in the deletion mutants. Our F. graminearum ΔH2A.Z mutant was indeed very slow-growing compared to its respective wild-type parental strain (Fig 1A).…”

Section: Knock-out Mutant Of Fgh2az Is Viable With Severe Defects Insupporting

confidence: 93%

Effect of H2A.Z deletion is rescued by compensatory mutations in Fusarium graminearum

Chen

Zehraoui

Atanasoff-Kardjalieff

et al. 2020

PLoS Genet

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Fusarium head blight is a destructive disease of grains resulting in reduced yields and contamination of grains with mycotoxins worldwide; Fusarium graminearum is its major causal agent. Chromatin structure changes play key roles in regulating mycotoxin biosynthesis in filamentous fungi. Using a split-marker approach in three F. graminearum strains INRA156, INRA349 and INRA812 (PH-1), we knocked out the gene encoding H2A.Z, a ubiquitous histone variant reported to be involved in a diverse range of biological processes in yeast, plants and animals, but rarely studied in filamentous fungi. All ΔH2A.Z mutants exhibit defects in development including radial growth, sporulation, germination and sexual reproduction, but with varying degrees of severity between them. Heterogeneity of osmotic and oxidative stress response as well as mycotoxin production was observed in ΔH2A.Z strains. Adding-back wild-type H2A.Z in INRA349ΔH2A.Z could not rescue the phenotypes. Whole genome sequencing revealed that, although H2A.Z has been removed from the genome and the deletion cassette is inserted at H2A.Z locus only, mutations occur at other loci in each mutant regardless of the genetic background. Genes affected by these mutations encode proteins involved in chromatin remodeling, such as the helicase Swr1p or an essential subunit of the histone deacetylase Rpd3S, and one protein of unknown function. These observations suggest that H2A.Z and the genes affected by such mutations are part or the same genetic interaction network. Our results underline the genetic plasticity of F. graminearum facing detrimental gene perturbation. These findings suggest that intergenic suppressions rescue deleterious phenotypes in ΔH2A.Z strains, and that H2A.Z may be essential in F. graminearum. This assumption is further supported by the fact that H2A.Z deletion failed in another Fusarium spp., i.e., the rice pathogen Fusarium fujikuroi.

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Section: Knock-out Mutant Of Fgh2az Is Viable With Severe Defects Insupporting

confidence: 93%

Effect of H2A.Z deletion is rescued by compensatory mutations in Fusarium graminearum

Chen

Zehraoui

Atanasoff-Kardjalieff

et al. 2020

PLoS Genet

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“…In addition, the backcrossed Δ hH2Az strain displayed slow and variable growth (Figure S2) and was hypersensitive to the DNA damaging agent MMS. This is consistent with previous studies that have demonstrated poor growth of Δ hH2Az in S. cerevisiae and in N. crassa (68, 69).…”

Section: Resultssupporting

confidence: 93%

“…This complemented defects in growth and MMS-sensitivity, and fully restored H3K27 methylation, suggesting loss of H2A.Z was responsible for all observed phenotypes in the deletion mutant (Figure 1C and 1D, S2). Because a specific chromatin remodeling complex, SWR1, exchanges H2A.Z for H2A in plants, yeast and animals (69-73), we next examined H3K27me2/3 in a deletion strain lacking the N. crassa homolog of the SWR1 ATPase (Δ swr-1) . The swr-1 mutant displayed a similar reduction in H3K27me2/3 (Figure 1C and D).…”

Section: Resultsmentioning

confidence: 99%

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The histone variant H2A.Z is required to establish normal patterns of H3K27 methylation inNeurospora crassa

Courtney¹,

Kamei²,

Ferraro³

et al. 2020

Preprint

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25 Neurospora crassa contains a minimal Polycomb repression system, which provides rich 26 opportunities to explore Polycomb-mediated repression across eukaryotes and enables genetic 27 studies that can be difficult in plant and animal systems. Polycomb Repressive Complex 2 is a 28 multi-subunit complex that deposits mono-, di-, and tri-methyl groups on lysine 27 of histone 29 H3, and tri-methyl H3K27 is a molecular marker of transcriptionally repressed facultative 30 heterochromatin. In mouse embryonic stem cells and multiple plant species, H2A.Z has been 31 found to be co-localized with H3K27 methylation. H2A.Z is required for normal H3K27 32 methylation in these experimental systems, though the regulatory mechanisms are not well 33 understood. We report here that Neurospora crassa mutants lacking H2A.Z or SWR-1, the ATP-34 dependent histone variant exchanger, exhibit a striking reduction in levels of H3K27 35 methylation. RNA-sequencing revealed downregulation of eed, encoding a subunit of PRC2, in 36 an hH2Az mutant compared to wild type and overexpression of EED in a ∆hH2Az;∆eed 37 background restored most H3K27 methylation. Reduced eed expression leads to region-specific 38 losses of H3K27 methylation suggesting that EED-dependent mechanisms are critical for normal 39 H3K27 methylation at certain regions in the genome. 40 41 42 43 44 45 46 In eukaryotes, DNA-dependent processes in the nucleus are regulated by chromatin-67 based mechanisms (1). One heavily studied group of proteins that are particularly important for 68 maintaining stable gene repression are the Polycomb Group (PcG) proteins. In plants and animal 69 cells, PcG proteins assemble into Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2), 70 which play key roles in repression of developmental genes, as reviewed in (2-6). PRC2 is a 71 multi-subunit complex that deposits mono-, di-, and tri-methyl groups on lysine 27 of histone 72 H3, and tri-methyl H3K27 is a molecular marker of transcriptionally repressed facultative 73 heterochromatin (7-10). PcG proteins are absent from the model yeasts, Saccharomyces 74 cerevisiae and Schizosaccharomyces pombe, but core PRC2 components have been identified 75 and characterized in several fungi, including Neurospora crassa, Fusarium graminearum, 76 Cryptococcus neoformans, Epichloë festucae, and Fusarium fujikoroi (11)(12)(13)(14)(15)(16)(17). In these fungi, 77 PRC2 is required for repression of key fungal genes suggesting that this enzyme complex is 78 functionally conserved between fungi, plants, and animals (13, 14, 18). 79In N. crassa, the catalytic subunit of PRC2 is SET-7, a protein with homology to 80 EZH1/EZH2 in humans and curly leaf (CLF), medea (MEA), or swinger (SWN) in Arabidopsis 81 (9, 10,(19)(20)(21)(22)(23)(24)(25). N. crassa EED and SUZ12 are respectively homologous to Drosophila Esc and 82 su(z)12, human EED and SUZ12, and Arabidopsis fertilization independent endosperm (FIE; a 83 homolog of EED), and SUZ12 homologs embryonic flower 2 (EMF2), vernalization 2 (VER2), 84 or fertilization in...

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“…Moreover, histone modifications are modulated by PER and CRY binding [72]. Similar cellular mechanisms have been described in the Neurospora clock [84].…”

Section: Possible Mechanisms Of Switch-like Inhibitionsupporting

confidence: 54%

Amplitude effects allow short jetlags and large seasonal phase shifts in minimal clock models

Ananthasubramaniam

Schmal

Herzel

2019

Preprint

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Mathematical models of varying complexity have helped shed light on different aspects of circadian clock function. In this work, we question whether minimal clock models (Goodwin models) are sufficient to reproduce essential phenotypes of the clock: a small phase response curve (PRC), fast jetlag and seasonal phase shifts. Instead of building a single best model, we take an approach where we study the properties of a set of models satisfying certain constraints; here a PRC to a one-hour pulse of three hours and clock periods between 22h and 26h. Surprisingly, almost all these randomly parameterized models showed a phase shift of about four hours between long and short days and jetlag durations of three to seven days in advance and delay. Moreover, intrinsic clock period influenced jetlag duration and entrainment amplitude and phase. Fast jetlag was realized in this model by means of a novel amplitude effect: the association between clock amplitude and clock period termed 'twist'. This twist allows amplitude changes to speed up and slow down clocks enabling faster shifts. These findings were robust to the addition of additional positive feedback to the model. In summary, the known design principles of rhythm generation -negative feedback, long delay and switch-like inhibition (we review these in detail) -are sufficient to reproduce the essential clock phenotypes. Furthermore, amplitudes play a role in determining clock properties and must be always considered, although they are difficult to measure.

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DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition

Cited by 24 publications

References 75 publications

Effect of H2A.Z deletion is rescued by compensatory mutations in Fusarium graminearum

Effect of H2A.Z deletion is rescued by compensatory mutations in Fusarium graminearum

The histone variant H2A.Z is required to establish normal patterns of H3K27 methylation inNeurospora crassa

Amplitude effects allow short jetlags and large seasonal phase shifts in minimal clock models

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