Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.

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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.

説明

<jats:p>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 &gt; 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.</jats:p>

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