Skip to content. | Skip to navigation

Personal tools

Sections
You are here: Home / Teams / Physical Biology of Chromatin - D. Jost / Publications / How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes.

How epigenome drives chromatin folding and dynamics, insights from efficient coarse-grained models of chromosomes.

Surya K Ghosh and Daniel Jost (2018)

PLoS Comput Biol, 14(5):e1006159.

The 3D organization of chromosomes is crucial for regulating gene expression andcell function. Many experimental and polymer modeling efforts are dedicated to deciphering the mechanistic principles behind chromosome folding. Chromosomes are long and densely packed-topologically constrained-polymers. The main challenges are therefore to develop adequate models and simulation methods to investigate properly the multi spatio-temporal scales of such macromolecules. Here, we proposed a generic strategy to develop efficient coarse-grained models for self-avoiding polymers on a lattice. Accounting accurately for the polymer entanglement length and the volumic density, we show that our simulation scheme not only captures the steady-state structural and dynamical properties of the system but also tracks the same dynamics at different coarse-graining. This strategy allows a strong power-law gain in numerical efficiency and offers a systematic way to define reliable coarse-grained null models for chromosomes andto go beyond the current limitations by studying long chromosomes during an extended time period with good statistics. We use our formalism to investigate in details the time evolution of the 3D organization of chromosome 3R (20 Mbp) in drosophila during one cell cycle (20 hours). We show that a combination of our coarse-graining strategy with a one-parameter block copolymer model integrating epigenomic-driven interactions quantitatively reproduce experimental data at thechromosome-scale and predict that chromatin motion is very dynamic during the cell cycle.

 
automatic medline import

Document Actions