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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  FEMS Microbiology Reviews Vol. 47, No. 3 ( 2023-05-19)
    In: FEMS Microbiology Reviews, Oxford University Press (OUP), Vol. 47, No. 3 ( 2023-05-19)
    Abstract: Comparative genomics has recently provided unprecedented insights into the biology and evolution of the fungal lineage. In the postgenomics era, a major research interest focuses now on detailing the functions of fungal genomes, i.e. how genomic information manifests into complex phenotypes. Emerging evidence across diverse eukaryotes has revealed that the organization of DNA within the nucleus is critically important. Here, we discuss the current knowledge on the fungal genome organization, from the association of chromosomes within the nucleus to topological structures at individual genes and the genetic factors required for this hierarchical organization. Chromosome conformation capture followed by high-throughput sequencing (Hi-C) has elucidated how fungal genomes are globally organized in Rabl configuration, in which centromere or telomere bundles are associated with opposite faces of the nuclear envelope. Further, fungal genomes are regionally organized into topologically associated domain-like (TAD-like) chromatin structures. We discuss how chromatin organization impacts the proper function of DNA-templated processes across the fungal genome. Nevertheless, this view is limited to a few fungal taxa given the paucity of fungal Hi-C experiments. We advocate for exploring genome organization across diverse fungal lineages to ensure the future understanding of the impact of nuclear organization on fungal genome function.
    Type of Medium: Online Resource
    ISSN: 1574-6976
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1500468-5
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  • 2
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 12, No. 5 ( 2022-05-06)
    Abstract: The eukaryotic genome must be precisely organized for its proper function, as genome topology impacts transcriptional regulation, cell division, replication, and repair, among other essential processes. Disruptions to human genome topology can lead to diseases, including cancer. The advent of chromosome conformation capture with high-throughput sequencing (Hi-C) to assess genome organization has revolutionized the study of nuclear genome topology; Hi-C has elucidated numerous genomic structures, including chromosomal territories, active/silent chromatin compartments, Topologically Associated Domains, and chromatin loops. While low-resolution heatmaps can provide important insights into chromosomal level contacts, high-resolution Hi-C datasets are required to reveal folding principles of individual genes. Of particular interest are high-resolution chromosome conformation datasets of organisms modeling the human genome. Here, we report the genome topology of the fungal model organism Neurospora crassa at a high resolution. Our composite Hi-C dataset, which merges 2 independent datasets generated with restriction enzymes that monitor euchromatin (DpnII) and heterochromatin (MseI), along with our DpnII/MseI double digest dataset, provide exquisite detail for both the conformation of entire chromosomes and the folding of chromatin at the resolution of individual genes. Within constitutive heterochromatin, we observe strong yet stochastic internal contacts, while euchromatin enriched with either activating or repressive histone post-translational modifications associates with constitutive heterochromatic regions, suggesting intercompartment contacts form to regulate transcription. Consistent with this, a strain with compromised heterochromatin experiences numerous changes in gene expression. Our high-resolution Neurospora Hi-C datasets are outstanding resources to the fungal community and provide valuable insights into higher organism genome topology.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2629978-1
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  • 3
    In: Genetics, Oxford University Press (OUP), Vol. 216, No. 3 ( 2020-11-01), p. 671-688
    Abstract: DNA methylation, a prototypical epigenetic modification implicated in gene silencing, occurs in many eukaryotes and plays a significant role in the etiology of diseases such as cancer. The filamentous fungus Neurospora crassa places DNA methylation at regions of constitutive heterochromatin such as in centromeres and in other A:T-rich regions of the genome, but this modification is dispensable for normal growth and development. This and other features render N. crassa an excellent model to genetically dissect elements of the DNA methylation pathway. We implemented a forward genetic selection on a massive scale, utilizing two engineered antibiotic-resistance genes silenced by DNA methylation, to isolate mutants defective in methylation (dim). Hundreds of potential mutants were characterized, yielding a rich collection of informative alleles of 11 genes important for DNA methylation, most of which were already reported. In parallel, we characterized the pairwise interactions in nuclei of the DCDC, the only histone H3 lysine 9 methyltransferase complex in Neurospora, including those between the DIM-5 catalytic subunit and other complex members. We also dissected the N- and C-termini of the key protein DIM-7, required for DIM-5 histone methyltransferase localization and activation. Lastly, we identified two alleles of a novel gene, dim-10 – a homolog of Clr5 in Schizosaccharomyces pombe – that is not essential for DNA methylation, but is necessary for repression of the antibiotic-resistance genes used in the selection, which suggests that both DIM-10 and DNA methylation promote silencing of constitutive heterochromatin.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 4
    In: Genetics, Oxford University Press (OUP), Vol. 211, No. 2 ( 2019-02-01), p. 563-578
    Abstract: In the filamentous fungus Neurospora crassa, constitutive heterochromatin is marked by tri-methylation of histone H3 lysine 9 (H3K9me3) and DNA methylation. We identified mutations in the Neurospora defective in methylation-1 (dim-1) gene that cause defects in cytosine methylation and implicate a putative AAA-ATPase chromatin remodeler. Although it was well-established that chromatin remodelers can affect transcription by influencing DNA accessibility with nucleosomes, little was known about the role of remodelers on chromatin that is normally not transcribed, including regions of constitutive heterochromatin. We found that dim-1 mutants display both reduced DNA methylation in heterochromatic regions as well as increased DNA methylation and H3K9me3 in some intergenic regions associated with highly expressed genes. Deletion of dim-1 leads to atypically spaced nucleosomes throughout the genome and numerous changes in gene expression. DIM-1 localizes to both heterochromatin and intergenic regions that become hyper-methylated in dim-1 strains. Our findings indicate that DIM-1 normally positions nucleosomes in both heterochromatin and euchromatin and that the standard arrangement and density of nucleosomes is required for the proper function of heterochromatin machinery.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2009
    In:  The FASEB Journal Vol. 23, No. S1 ( 2009-04)
    In: The FASEB Journal, Wiley, Vol. 23, No. S1 ( 2009-04)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Elsevier BV ; 2003
    In:  Insect Biochemistry and Molecular Biology Vol. 33, No. 9 ( 2003-9), p. 853-863
    In: Insect Biochemistry and Molecular Biology, Elsevier BV, Vol. 33, No. 9 ( 2003-9), p. 853-863
    Type of Medium: Online Resource
    ISSN: 0965-1748
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 1483248-3
    SSG: 12
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