Zimatore Giovanna, Tsuchiya Masa, Hashimoto Midori, Kasperski Andrzej, Giuliani Alessandro
eCampus University, 22060 Novedrate, Como, Italy and CNR-IMM Bologna, Italy.
SEIKO Life Science Laboratory, SEIKO Research Institute for Education, Osaka 540-659, Japan.
Biophys Rev (Melville). 2021 Sep 21;2(3):031303. doi: 10.1063/5.0058511. eCollection 2021 Sep.
The human DNA molecule is a 2-m-long polymer collapsed into the micrometer space of the cell nucleus. This simple consideration rules out any "Maxwell demon"-like explanation of regulation in which a single regulatory molecule (e.g., a transcription factor) finds autonomously its way to the particular target gene whose expression must be repressed or enhanced. A gene-by-gene regulation is still more contrasting with the physical reality when in the presence of cell state transitions involving the contemporary expression change of thousands of genes. This state of affair asks for a statistical mechanics inspired approach where specificity arises from a selective unfolding of chromatin driving the rewiring of gene expression pattern. The arising of "expression waves" marking state transitions related to chromatin structural reorganization through self-organized critical control of whole-genome expression will be described in the present paper. We adopt as a model system the gene expression time course of a cancer cell (MCF-7) population exposed to an efficient stimulus causing a state transition in comparison with an ineffective stimulus. The obtained results will be put into the perspective of biological adaptive systems living on the edge of chaos.
人类DNA分子是一种长达2米的聚合物,折叠在细胞核的微米级空间中。这一简单的考量排除了任何类似“麦克斯韦妖”的调控解释,即在这种解释中,单个调控分子(如转录因子)能自主找到其必须抑制或增强表达的特定靶基因。当存在涉及数千个基因同时表达变化的细胞状态转变时,逐个基因的调控与物理现实的矛盾就更加突出。这种情况需要一种受统计力学启发的方法,其中特异性源于染色质的选择性解折叠,驱动基因表达模式的重新布线。本文将描述通过对全基因组表达的自组织临界控制,标记与染色质结构重组相关的状态转变的“表达波”的出现。我们采用癌细胞(MCF-7)群体的基因表达时间进程作为模型系统,该群体暴露于一种有效的刺激下会导致状态转变,同时与无效刺激进行比较。所获得的结果将从生活在混沌边缘的生物自适应系统的角度进行阐述。