Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains.
Bottom Line: Remarkably, recent studies indicate that these 1D epigenomic domains tend to fold into 3D topologically associated domains forming specialized nuclear chromatin compartments.We show how experiments are fully consistent with multistable conformations where topologically associated domains of the same epigenomic state interact dynamically with each other.Our approach provides a general framework to improve our understanding of chromatin folding during cell cycle and differentiation and its relation to epigenetics.
Affiliation: Laboratoire de Physique, Ecole Normale Supérieure de Lyon, CNRS UMR 5672, Lyon 69007, France.Show MeSH
Mentions: We model the chromatin fiber as an interacting self-avoiding bead-and-spring chain. Each monomer represents a portion of DNA (10 kb) and is characterized by an epigenetic state (see Figure 1). In addition to standard excluded volume interactions, we consider attractive short-range interactions Emn between monomers. In the following, we assume only two types of interactions: (i) non-specific interactions Uns between every pairs of monomers that effectively account for compaction effect due to confinement into the nucleus; and (ii) specific attractive interactions Us between monomers having the same epigenetic state (Figure 1). Hence Emn = Uns+ δmnUs with δmn = 1 (resp. 0) if monomers m and n have (resp. have not) the same epigenetic state.
Affiliation: Laboratoire de Physique, Ecole Normale Supérieure de Lyon, CNRS UMR 5672, Lyon 69007, France.