title: Emergent Self-Organized Criticality in Gene Expression Dynamics: Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line.
abstract: BACKGROUND
  The underlying mechanism of dynamic control of the genome-wide expression is a fundamental issue in bioscience. We addressed it in terms of phase transition by a systemic approach based on both density analysis and characteristics of temporal fluctuation for the time-course mRNA expression in differentiating MCF-7 breast cancer cells.
  
  
  METHODS
  In a recent work, we suggested criticality as an essential aspect of dynamic control of genome-wide gene expression. Criticality was evident by a unimodal-bimodal transition through flattened unimodal expression profile. The flatness on the transition suggests the existence of a critical transition at which up- and down-regulated expression is balanced. Mean field (averaging) behavior of mRNAs based on the temporal expression changes reveals a sandpile type of transition in the flattened profile. Furthermore, around the transition, a self-similar unimodal-bimodal transition of the whole expression occurs in the density profile of an ensemble of mRNA expression. These singular and scaling behaviors identify the transition as the expression phase transition driven by self-organized criticality (SOC).
  
  
  RESULTS
  Emergent properties of SOC through a mean field approach are revealed: i) SOC, as a form of genomic phase transition, consolidates distinct critical states of expression, ii) Coupling of coherent stochastic oscillations between critical states on different time-scales gives rise to SOC, and iii) Specific gene clusters (barcode genes) ranging in size from kbp to Mbp reveal similar SOC to genome-wide mRNA expression and ON-OFF synchronization to critical states. This suggests that the cooperative gene regulation of topological genome sub-units is mediated by the coherent phase transitions of megadomain-scaled conformations between compact and swollen chromatin states.
  
  
  CONCLUSIONS
  In summary, our study provides not only a systemic method to demonstrate SOC in whole-genome expression, but also introduces novel, physically grounded concepts for a breakthrough in the study of biological regulation.
authors.affiliation: Systems Biology Program, School of Media and Governance, Keio University, Fujisawa, Japan.
authors.forename: Masa
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Environment and Health Department, Istituto Superiore di Sanitá, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giuliani
authors.affiliation: Graduate School of Frontier Science, The University of Tokyo, Kashiwa, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Latvian Biomedical Research & Study Centre, Riga, Latvia.
authors.forename: Jekaterina
authors.initials: J
authors.lastname: Erenpreisa
authors.affiliation: Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D003198:Computer Simulation; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D061986:MCF-7 Cells; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D059467:Transcriptome
chemical_list: D020890:Neuregulin-1; D012333:RNA, Messenger; D004815:Epidermal Growth Factor