Résumé:

Gene expression program in eukaryotic cells is strongly dependent on physical state of the genome carrier. Physical state of the chromatin fiber constituting chromosomes is a key element in this program. However, despite the efforts to elucidate the structure and physical principles underlying chromatin organization, they remain not clear. On the one hand, chromosomes are highly hierarchical structures with quite different interactions involved on different scales of organization. On the other hand, the interactions involved at each scale are extremely complex (e.g. at 30 nm scale these are direct electrostatic, solvent mediated structural and polyelectrolyte mediated bridging interactions, DNA tension, etc.). Usual approach consisting in taking into account all the interactions between various molecular elements on the microscopic scale remains in this case out of reach. In the present work we suggest the approach which studies mesoscopic properties of the chromatin components and their interactions. Corresponding phenomenological theory helps to analyze the thermodynamically probable chromatin organization. We focus on liquid-crystalline order in chromatin resulting from the balance of thermal disorder and electrostatic (and mechanical) interactions. Using generally accepted experimental facts we identify robust mesogenic parameters of nucleosomes (DNA-protein nanoassemblies) at the smaller scale and show how the correlations of these parameters control the ordering into a chromatin structure at the bigger scale. The model is based on correlation of polar and chiral characteristics of nucleosomes. Phenomenological theory allows us to describe the condensed phases in aqueous solutions of nucleosomes with digested linker DNA, both in physiological conditions and in a wide range of monovalent salt concentration. Using the hypothesis of similar physical mechanism acting in condensed solutions and in the fiber in the same physiological conditions, we perform detailed symmetry analysis, construct the free energy model and reveal the thermodynamically favorable helical liquid-crystalline states of the fiber. In addition to « solenoid » and « two-start-helix » models abundantly discussed previously, we show the possibility of multi-start helix arrangements of nucleosomes in the chromatin and possible biaxiality of the structures. The effects of homogeneous mechanical force field applied to the chromatin in biochemical experiments are also studied. We show that helical state unwinding is a multi-step process and we give its structural and thermodynamic details.