Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.
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.
Yokota
H
H
Department of Molecular Biotechnology, University of Washington, Seattle 98195, USA.
van den Engh
G
G
Hearst
J E
JE
Sachs
R K
RK
Trask
B J
BJ
D002453:Cell Cycle / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics / Q000648:ultrastructure; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure*; D002875:Chromosomes / Q000648:ultrastructure*; D004247:DNA / Q000648:ultrastructure*; D005260:Female; D005347:Fibroblasts / Q000648:ultrastructure; D016193:G1 Phase; D006801:Humans; D016192:Resting Phase, Cell Cycle
D002843:Chromatin; D004247:DNA