Fig. 2.

A diagram of the Mi-2/NuRD and multiple-tier cancer attractors and “mountain and valley” metaphor. A hypothetical epigenetic landscape to illustrate the concepts behind the hierarchy of cell type diversification during worm embryo and early larvae development that is regulated by NuRDs, alongside with the notions of “attractor” and basin of attraction by “mountain and valley” analogy. In a two-dimensional representation, the X-axis is a “state space”; the Y-axis (quasi-potential, inverse of probability) represents the relative instability of individual states at each state-space location. The “X” in red means the “loss of function” defect in NuRDs. Basins at top lake and bottom valley correspond to stable equilibrium (equilibrium attractors). Normally, minimal internal fluctuation or external perturbations will move the oval marbles (i.e., cells) away from unstable points (i.e., points at brisk of basins), while the oval marble will generally return to its attractors within its basin of attraction, even under the action of more important perturbations. However, major “potential” energy transfers (e.g., the “lightning”, hereby metaphorically caused by “loss of function” of the major controller of germline stem cell–soma distinction, i.e., NuRD) will be able to induce an oval marbles jumping out of its basin of attraction (i.e., differentiated cell “valley”) and being pushed up and then trapped by another attractor (e.g., the stem-cell “lake” or progenitor cell “basin”). In general, the meta-stable state (e.g., progenitor cell) is a weak attractor from which the oval marble may relatively easily reach a neighboring stable attractor. Note : “=” in figure is “~”, an approximation. This analogy is simplified. Multiple levels of “valleys” indicate the different levels of toti-/pluri-/multi-/mono-/potency, which are likely regulated by NuRD/CRCs. In other exceptional contexts, NuRD might inhibit the potential of differentiation