  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.
