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      Nuclear genome organization in fungi: from gene folding to Rabl chromosomes

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          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.

          Abstract

          Within the nucleus, fungal genomes are organized hierarchically, from the association of chromosomes to topological structures at individual genes, and this organization directly impacts genome function.

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          Most cited references346

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          A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping.

          We use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs "facing" one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

            We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.
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              Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions

              The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories (CT), and numerous models have been proposed for how chromosomes fold within CTs 1 . These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid revolutions in the study of 3D genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide 2 . In the present study, we investigated the 3D organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term “topological domains”, as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, suggesting that topological domains are an inherent property of mammalian genomes. Lastly, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, tRNAs, and SINE retrotransposons, suggesting that these factors may play a role in establishing the topological domain structure of the genome.
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                Author and article information

                Contributors
                Journal
                FEMS Microbiol Rev
                FEMS Microbiol Rev
                femsre
                FEMS Microbiology Reviews
                Oxford University Press
                0168-6445
                1574-6976
                May 2023
                17 May 2023
                17 May 2023
                : 47
                : 3
                : fuad021
                Affiliations
                Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands
                Laboratory of Phytopathology, Wageningen University and Research ,Droevendaalsesteeg 4, 6708 PB Wageningen, The Netherlands
                Department of Chemistry and Biochemistry, University of Colorado Colorado Springs , 234 Centennial Hall, 1420 Austin Bluffs Pkwy, Colorado Springs, CO 80918 USA
                Department of Chemistry and Biochemistry, University of Colorado Colorado Springs , 234 Centennial Hall, 1420 Austin Bluffs Pkwy, Colorado Springs, CO 80918 USA
                Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University , Padualaan 8, 3584 CH Utrecht, The Netherlands
                Author notes
                Corresponding author. Andrew D. Klocko: Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, 234 Centennial Hall, 1420 Austin Bluffs Pkwy, Colorado Springs, CO 80918 USA. E-mail: aklocko@ 123456uccs.edu
                Corresponding author. Michael Seidl: Theoretical Biology and Bioinformatics, Department of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. E-mail: m.f.seidl@ 123456uu.nl

                These authors contributed equally

                Author information
                https://orcid.org/0000-0003-3711-0548
                https://orcid.org/0000-0003-2686-0183
                https://orcid.org/0000-0002-2236-672X
                https://orcid.org/0000-0002-5218-2083
                Article
                fuad021
                10.1093/femsre/fuad021
                10246852
                37197899
                d0e8fa1d-7992-4aa0-a91f-470c16ceac46
                © The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 February 2023
                : 28 April 2023
                : 08 May 2023
                : 07 June 2023
                Page count
                Pages: 22
                Funding
                Funded by: Consejo Nacional de Ciencia y Tecnología, DOI 10.13039/501100003141;
                Funded by: National Institutes of Health, DOI 10.13039/100000002;
                Award ID: 1R15GM140396-01
                Funded by: University of Colorado Colorado Springs, DOI 10.13039/100010175;
                Categories
                Review Article
                AcademicSubjects/SCI01150

                Microbiology & Virology
                fungi,3d genome organization,nuclear organization,topologically associated domain,chromosome conformation capture followed by high-throughput sequencing (hi-c)

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