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      Into the chromatin world: Role of nuclear architecture in epigenome regulation

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          Abstract

          Epigenome modifications are established early in development and differentiation and generate distinct levels of chromatin complexity. The specific position of chromosomes and the compaction state of chromatin are both typical features that make it possible to distinguish between repressive and permissive environment for gene expression. In this review we describe the distinct levels of epigenome structures, emphasizing the role of nuclear architecture in the control of gene expression. Recent novel insights have increasingly demonstrated that the nuclear environment can influence nuclear processes such as gene expression and DNA repair. These findings have revealed a further important aspect of the chromatin modifications, suggesting that a proper crosstalk between chromatin and nuclear components, such as lamins or nuclear pores, is required to ensure the correct functioning of the nucleus and that this assumes a crucial role in many pathologies and diseases. Knowledge regarding the molecular mechanisms behind most of these developmental and disease-related defects remains incomplete; the influence of the nuclear architecture on chromatin function may provide a new perspective for understanding these phenotypes.

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          A decade of 3C technologies: insights into nuclear organization.

          Over the past 10 years, the development of chromosome conformation capture (3C) technology and the subsequent genomic variants thereof have enabled the analysis of nuclear organization at an unprecedented resolution and throughput. The technology relies on the original and, in hindsight, remarkably simple idea that digestion and religation of fixed chromatin in cells, followed by the quantification of ligation junctions, allows for the determination of DNA contact frequencies and insight into chromosome topology. Here we evaluate and compare the current 3C-based methods (including 4C [chromosome conformation capture-on-chip], 5C [chromosome conformation capture carbon copy], HiC, and ChIA-PET), summarize their contribution to our current understanding of genome structure, and discuss how shape influences genome function.
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            Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer.

            Polycomb Group (PcG) proteins are transcriptional repressors that epigenetically modify chromatin and participate in the establishment and maintenance of cell fates. These proteins play important roles in both stem cell self-renewal and in cancer development. Our understanding of their mechanism of action has greatly advanced over the past 10 years, but many unanswered questions remain. In this review, we present the currently available experimental data that connect PcG protein function with some of the key processes which govern somatic stem cell activity. We also highlight recent studies suggesting that a delicate balance in PcG gene dosage is crucial for proper stem cell homeostasis and prevention of cancer stem cell development. Copyright 2010 Elsevier Inc. All rights reserved.
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              The epigenetic regulation of mammalian telomeres.

              Increasing evidence indicates that chromatin modifications are important regulators of mammalian telomeres. Telomeres provide well studied paradigms of heterochromatin formation in yeast and flies, and recent studies have shown that mammalian telomeres and subtelomeric regions are also enriched in epigenetic marks that are characteristic of heterochromatin. Furthermore, the abrogation of master epigenetic regulators, such as histone methyltransferases and DNA methyltransferases, correlates with loss of telomere-length control, and telomere shortening to a critical length affects the epigenetic status of telomeres and subtelomeres. These links between epigenetic status and telomere-length regulation provide important new avenues for understanding processes such as cancer development and ageing, which are characterized by telomere-length defects.
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                Author and article information

                Contributors
                Journal
                AIMS Biophysics
                AIMS Biophysics
                AIMS Press
                2377-9098
                29 October 2015
                : 2
                : 4
                : 585-612
                Affiliations
                [1 ] CNR Institute of Cell Biology and Neurobiology, IRCCS Santa Lucia Foundation, Via Del Fosso di Fiorano 64, Rome, Italy
                [2 ] Istituto Nazionale Genetica Molecolare Romeo ed Enrica Invernizzi, Via Francesco Sforza 35, Milan, Italy
                Author notes
                Chiara Lanzuolo, Email: chiara.lanzuolo@ 123456cnr.it ; Tel:+39-02-0066-0358; Fax:+ 39-02-0066-0216.
                Article
                10.3934/biophy.2015.4.585
                e4a47efa-e53c-4b1e-9d34-e0a4c4563083
                History
                : 27 July 2015
                : 25 October 2015
                Categories
                Review

                Biophysics
                chromatin higher order structures,nuclear architecture,Polycomb,gene expression regulation, compartmentalization

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