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Nucleus. 2016 Sep 2;7(5):453-461.

Simulating topological domains in human chromosomes with a fitting-free model.

Author information

a SUPA, School of Physics & Astronomy , University of Edinburgh , Edinburgh , UK.
b Department of Plant Sciences , University of Oxford , Oxford , UK.
c Sir William Dunn School of Pathology , University of Oxford , Oxford , UK.


We discuss a polymer model for the 3D organization of human chromosomes. A chromosome is represented by a string of beads, with each bead being "colored" according to 1D bioinformatic data (e.g., chromatin state, histone modification, GC content). Individual spheres (representing bi- and multi-valent transcription factors) can bind reversibly and selectively to beads with the appropriate color. During molecular dynamics simulations, the factors bind, and the string spontaneously folds into loops, rosettes, and topologically-associating domains (TADs). This organization occurs in the absence of any specified interactions between distant DNA segments, or between transcription factors. A comparison with Hi-C data shows that simulations predict the location of most boundaries between TADs correctly. The model is "fitting-free" in the sense that it does not use Hi-C data as an input; consequently, one of its strengths is that it can - in principle - be used to predict the 3D organization of any region of interest, or whole chromosome, in a given organism, or cell line, in the absence of existing Hi-C data. We discuss how this simple model might be refined to include more transcription factors and binding sites, and to correctly predict contacts between convergent CTCF binding sites.


Brownian dynamics simulations; Hi-C contact maps; chromosome organization; fitting-free models; nuclear bodies and intranuclear protein clusters

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