FORCES DRIVING CHROMATIN IN THE NUCLEUS

The physics of genome dynamics requires innovative out-of-equilibrium

approaches because the cell nucleus, from the most basic chemical reactions to

evolutionary timescales of billions of years, strives to counteract disorder in order

to be healthy, consuming energy, being alive. My objective is to develop a

physical theory able to describe intranuclear dynamics, with the ambition of

reaching a quantitative understanding of the two essential processes of gene

regulation and DNA recombination. In particular, I investigate: (i) how 3D

chromosome conformation is shaped by specific biological processes.

Particularly loop extrusion and the formation of foci - or phases - for

heterochromatin and transcription, and (ii) the fundamental implications of thee

mechanisms on control and reliability of the biological processes of transcriptional

induction, gene silencing, and evolution. In this talk I will present my original

approach to simulate loop extrusion, an active process central in regulating the

shape of chromatin in vivo. The "gold standard" currently uses molecular

dynamics simulations: while very flexible, this limits our possibility (i) to explore

the parameter space in an efficient manner and (ii) to dissect the observed effects

under the lenses of a coherent analytical theory. I will show my original approach

that exploits the analytical solution of the Einstein-Smoluchowski equation for the

Rouse model affected by the action of extruders simulated in 1D. The resulting

probability distributions highlight the hallmarks of the out-of-equilibrium

processes on chromatin conformation observed in vivo by experiments. Finally,

this approach permits the definition of the Gibbs entropy of chromosome

conformation. I will show how the application of this concept to simplified toymodels

increases our analytical understanding of the loop extrusion process.