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.