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      Chromosome positioning and male infertility: it comes with the territory

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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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            Beyond the sequence: cellular organization of genome function.

             Tom Misteli (2007)
            Genomes are more than linear sequences. In vivo they exist as elaborate physical structures, and their functional properties are strongly determined by their cellular organization. I discuss here the functional relevance of spatial and temporal genome organization at three hierarchical levels: the organization of nuclear processes, the higher-order organization of the chromatin fiber, and the spatial arrangement of genomes within the cell nucleus. Recent insights into the cell biology of genomes have overturned long-held dogmas and have led to new models for many essential cellular processes, including gene expression and genome stability.
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              Chromosome territories.

              Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenomics is considered, followed by a historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT architecture, and of structural interactions with other CTs is provided as well as the dynamics of CT arrangements during cell cycle and postmitotic terminal differentiation. The article concludes with a discussion of open questions and new experimental strategies to answer them.
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                Author and article information

                Journal
                Journal of Assisted Reproduction and Genetics
                J Assist Reprod Genet
                Springer Nature
                1058-0468
                1573-7330
                November 2018
                September 18 2018
                November 2018
                : 35
                : 11
                : 1929-1938
                Article
                10.1007/s10815-018-1313-3
                © 2018

                http://www.springer.com/tdm

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