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      Comparison of the three-dimensional organization of sperm and fibroblast genomes using the Hi-C approach

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          Abstract

          Background

          The three-dimensional organization of the genome is tightly connected to its biological function. The Hi-C approach was recently introduced as a method that can be used to identify higher-order chromatin interactions genome-wide. The aim of this study was to determine genome-wide chromatin interaction frequencies using the Hi-C approach in mouse sperm cells and embryonic fibroblasts.

          Results

          The obtained data demonstrate that the three-dimensional genome organizations of sperm and fibroblast cells show a high degree of similarity both with each other and with the previously described mouse embryonic stem cells. Both A- and B-compartments and topologically associated domains are present in spermatozoa and fibroblasts. Nevertheless, sperm cells and fibroblasts exhibit statistically significant differences between each other in the contact probabilities of defined loci. Tight packaging of the sperm genome results in an enrichment of long-range contacts compared with the fibroblasts. However, only 30% of the differences in the number of contacts are based on differences in the densities of their genome packages; the main source of the differences is the gain or loss of contacts that are specific for defined genome regions. We find that the dependence of the contact probability on genomic distance for sperm is close to the dependence predicted for the fractal globular folding of chromatin.

          Conclusions

          Overall, we can conclude that the three-dimensional structure of the genome is passed through generations without being dramatically changed in sperm cells.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13059-015-0642-0) contains supplementary material, which is available to authorized users.

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          Most cited references12

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          Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements.

          Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also identified a new looping interaction in K562 cells between the beta-globin Locus Control Region and the gamma-beta-globin intergenic region. Interestingly, this region has been implicated in the control of developmental globin gene switching. 5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure.
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            Organization of the mitotic chromosome.

            Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.
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              Genome architectures revealed by tethered chromosome conformation capture and population-based modeling.

              We describe tethered conformation capture (TCC), a method for genome-wide mapping of chromatin interactions. By performing ligations on solid substrates rather than in solution, TCC substantially enhances the signal-to-noise ratio, thereby facilitating a detailed analysis of interactions within and between chromosomes. We identified a group of regions in each chromosome in human cells that account for the majority of interchromosomal interactions. These regions are marked by high transcriptional activity, suggesting that their interactions are mediated by transcriptional machinery. Each of these regions interacts with numerous other such regions throughout the genome in an indiscriminate fashion, partly driven by the accessibility of the partners. As a different combination of interactions is likely present in different cells, we developed a computational method to translate the TCC data into physical chromatin contacts in a population of three-dimensional genome structures. Statistical analysis of the resulting population demonstrates that the indiscriminate properties of interchromosomal interactions are consistent with the well-known architectural features of the human genome.
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                Author and article information

                Contributors
                battulin@bionet.nsc.ru
                minja-f@ya.ru
                mazur.am@gmail.com
                pomaznoy@gmail.com
                anya.khabarova@gmail.com
                ada@bionet.nsc.ru
                prokhortchouk@gmail.com
                serov@bionet.nsc.ru
                Journal
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1465-6906
                1465-6914
                14 April 2015
                14 April 2015
                2015
                : 16
                : 1
                : 77
                Affiliations
                [ ]Institute of Cytology and Genetics, Novosibirsk, 630090 Russia
                [ ]Novosibirsk State University, Novosibirsk, 630090 Russia
                [ ]Center ‘Bioengineering’, Russian Academy of Sciences, Moscow, 117312 Russia
                [ ]National Research Center, Kurchatov Institute, Moscow, 123098 Russia
                [ ]Skoltech Center for Stem Cell Research, Skolkovo Institute of Science and Technology, Skolkovo 143025, Moscow, Russia
                Article
                642
                10.1186/s13059-015-0642-0
                4434584
                25886366
                a2ac7f1c-330f-4db2-a953-6dbead3ff37f
                © Battulin et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 December 2014
                : 23 March 2015
                Categories
                Research
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                © The Author(s) 2015

                Genetics
                Genetics

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