  The architecture of the eukaryotic genome is characterized by a high degree
of spatial organization. Chromosomes occupy preferred territories correlated to
their state of activity and, yet, displace their genes to interact with remote
sites in complex patterns requiring the orchestration of a huge number of DNA
loci and molecular regulators. Far from random, this organization serves
crucial functional purposes, but its governing principles remain elusive. By
computer simulations of a Statistical Mechanics model, we show how
architectural patterns spontaneously arise from the physical interaction
between soluble binding molecules and chromosomes via collective thermodynamics
mechanisms. Chromosomes colocalize, loops and territories form and find their
relative positions as stable thermodynamic states. These are selected by
"thermodynamic switches" which are regulated by concentrations/affinity of
soluble mediators and by number/location of their attachment sites along
chromosomes. Our "thermodynamic switch model" of nuclear architecture, thus,
explains on quantitative grounds how well known cell strategies of upregulation
of DNA binding proteins or modification of chromatin structure can dynamically
shape the organization of the nucleus.
