Blog
About

27
views
0
recommends
+1 Recommend
1 collections
    1
    shares
      • Record: found
      • Abstract: found
      • Article: found

      How the Genome Folds: The Biophysics of Four-Dimensional Chromatin Organization

      1 , 1 , 2 , 3 , 1

      Annual Review of Biophysics

      Annual Reviews

      Read this article at

      ScienceOpenPublisher
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The genetic information that instructs transcription and other cellular functions is carried by the chromosomes, polymers of DNA in complex with histones and other proteins. These polymers are folded inside nuclei five orders of magnitude smaller than their linear length, and many facets of this folding correlate with or are causally related to transcription and other cellular functions. Recent advances in sequencing and imaging-based techniques have enabled new views into several layers of chromatin organization. These experimental findings are accompanied by computational modeling efforts based on polymer physics that can provide mechanistic insights and quantitative predictions. Here, we review current knowledge of the main levels of chromatin organization, from the scale of nucleosomes to the entire nucleus, our current understanding of their underlying biophysical and molecular mechanisms, and some of their functional implications.

          Related collections

          Most cited references 63

          • Record: found
          • Abstract: found
          • Article: not found

          The multifunctional nucleolus.

          The nucleolus is a distinct subnuclear compartment that was first observed more than 200 years ago. Nucleoli assemble around the tandemly repeated ribosomal DNA gene clusters and 28S, 18S and 5.8S ribosomal RNAs (rRNAs) are transcribed as a single precursor, which is processed and assembled with the 5S rRNA into ribosome subunits. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now show that it has additional functions. Some of these functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response and biogenesis of multiple ribonucleoprotein particles, will be discussed, as will the relation of the nucleolus to human diseases.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Differences in the Localization and Morphology of Chromosomes in the Human Nucleus

              Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized.
                Bookmark

                Author and article information

                Journal
                Annual Review of Biophysics
                Annu. Rev. Biophys.
                Annual Reviews
                1936-122X
                1936-1238
                May 06 2019
                May 06 2019
                : 48
                : 1
                : 231-253
                Affiliations
                [1 ]Unité Imagerie et Modélisation, CNRS UMR 3691, and C3BI (Center of Bioinformatics, Biostatistics and Integrative Biology), CNRS USR 3756, Institut Pasteur, 75015 Paris, France;, ,
                [2 ]Sorbonne Universités, CNRS, 75005 Paris, France
                [3 ]Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, and CIRM Center of Excellence in Stem Cell Genomics, University of California, Berkeley, California 94720, USA
                Article
                10.1146/annurev-biophys-052118-115638
                © 2019

                Comments

                Comment on this article