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Cell cycle control based on switching of chromatin domain sets
Nuclear organisation and gene expression (735-761)
735
736
CELL CYCLE CONTROL BASED ON SWITCHING OF C}ROMATINDOMAIN SETS Andreev, S.G. Moscow Physical Engineering Institute, Moscow, 115409, USS~ It is assumed that cooperative transitions of higher-order chromatin structure between discrete dynamical states may be important for understanding the cell-cycle and developmental specific genes control. In a sense these transitions are analogous the phase transitions. For this reason they may coordinate looping and dislooping of chromatin domains in the nucleous and hence be responsible for spatial and temporal ordering of genes switching. Supercoiling as well as nuclear matrix assembly-disassembly, spontaneous DNA strand breaks are the various pathways to alter or to maintain both chromatin states (domain sets) and transitions intensity between them. It is known from experiments that genome reprogramming in vivo does not require DNA sythesis, and cell growth arrest does not link directly to differentiatio~ These findings may be accounted for in terms of ordered switching of chromatindomainsets during the GI phase of cell cycle. This explanation is also fit to other problems, such as the choise of differentiation "direction" for pluripotent cells, the differentiation in fixed "direction" to terminal state, the ability of cell roundergo reversible t~ansitions to ~he rest nondividing state GO (or Gs), the existence of reversible and irreversible states of differentiation (Gd). The explanation is theoretically supported by calculations of energy required for chromatin looping, for repressed-active domain structure transition and also by recent experimental date.
INFRINGEM~Vr OF ORDERED SWITCHING OF C~qROMATIN DOMAIN SETS MAY UNDERLIE INITIAL STEPS OF CELL MALIGNIZATION Andreev, S.G. Moscow Physical Engineering Institute, Kashirskoe, Moscow, U.S.S.~ The ability to integrally control cellular differentiation and proliferation is associated in the model with cooperative integrity properties and transitions of supramolecularchromatin structure. Coordinated looping-dislooping of domains in various chromatin zones during GI phase of cell cycle is one of most critical points of preneoplasia. The possible mechanism to infringe Iooping-dislooping process is that chromatin architecture harding increases. Other mechanism of partial or completely disorder of chromatin domain sets switching deals with destahilization or loosening of supramolecular chromatln structure at any phase of cell cycle. In this scenario the probability of oncogene expression may be predicted. The model allows to explain, why decrease of mean loop size and increase of mean supercoiled density, as well as DNA-protein interactions weakness are ofter observed during the malignant transformation of the cells.
$218
735
736
CELL CYCLE CONTROL BASED ON SWITCHING OF C}ROMATINDOMAIN SETS Andreev, S.G. Moscow Physical Engineering Institute, Moscow, 115409, USS~ It is assumed that cooperative transitions of higher-order chromatin structure between discrete dynamical states may be important for understanding the cell-cycle and developmental specific genes control. In a sense these transitions are analogous the phase transitions. For this reason they may coordinate looping and dislooping of chromatin domains in the nucleous and hence be responsible for spatial and temporal ordering of genes switching. Supercoiling as well as nuclear matrix assembly-disassembly, spontaneous DNA strand breaks are the various pathways to alter or to maintain both chromatin states (domain sets) and transitions intensity between them. It is known from experiments that genome reprogramming in vivo does not require DNA sythesis, and cell growth arrest does not link directly to differentiatio~ These findings may be accounted for in terms of ordered switching of chromatindomainsets during the GI phase of cell cycle. This explanation is also fit to other problems, such as the choise of differentiation "direction" for pluripotent cells, the differentiation in fixed "direction" to terminal state, the ability of cell roundergo reversible t~ansitions to ~he rest nondividing state GO (or Gs), the existence of reversible and irreversible states of differentiation (Gd). The explanation is theoretically supported by calculations of energy required for chromatin looping, for repressed-active domain structure transition and also by recent experimental date.
INFRINGEM~Vr OF ORDERED SWITCHING OF C~qROMATIN DOMAIN SETS MAY UNDERLIE INITIAL STEPS OF CELL MALIGNIZATION Andreev, S.G. Moscow Physical Engineering Institute, Kashirskoe, Moscow, U.S.S.~ The ability to integrally control cellular differentiation and proliferation is associated in the model with cooperative integrity properties and transitions of supramolecularchromatin structure. Coordinated looping-dislooping of domains in various chromatin zones during GI phase of cell cycle is one of most critical points of preneoplasia. The possible mechanism to infringe Iooping-dislooping process is that chromatin architecture harding increases. Other mechanism of partial or completely disorder of chromatin domain sets switching deals with destahilization or loosening of supramolecular chromatln structure at any phase of cell cycle. In this scenario the probability of oncogene expression may be predicted. The model allows to explain, why decrease of mean loop size and increase of mean supercoiled density, as well as DNA-protein interactions weakness are ofter observed during the malignant transformation of the cells.
$218