We determined the folding of chromosomes in interphase nuclei by measuring the distance between points on the same chromosome. Over 25,000 measurements were made in G0/G1 nuclei between DNA sequences separated by 0.15-190 megabase pairs (Mbp) on three human chromosomes. The DNA sequences were specifically labeled by fluorescence in situ hybridization. The relationship between mean-square interphase distance and genomic separation has two linear phases, with a transition at approximately 2 Mbp. This biphasic relationship indicates the existence of two organizational levels at scales > 100 kbp. On one level, chromatin appears to be arranged in large loops several Mbp in size. Within each loop, chromatin is randomly folded. On the second level, specific loop-attachment sites are arranged to form a supple, backbonelike structure, which also shows characteristic random walk behavior. This random walk/giant loop model is the simplest model that fully describes the observed large-scale spatial relationships. Additional evidence for large loops comes from measurements among probes in Xq28, where interphase distance increases and then locally decreases with increasing genomic separation.
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September 15 1995
Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.
H Yokota,
H Yokota
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
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G van den Engh,
G van den Engh
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
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J E Hearst,
J E Hearst
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
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R K Sachs,
R K Sachs
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
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B J Trask
B J Trask
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
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H Yokota
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
G van den Engh
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
J E Hearst
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
R K Sachs
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
B J Trask
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1995) 130 (6): 1239–1249.
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H Yokota, G van den Engh, J E Hearst, R K Sachs, B J Trask; Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.. J Cell Biol 15 September 1995; 130 (6): 1239–1249. doi: https://doi.org/10.1083/jcb.130.6.1239
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