tailieunhanh - Báo cáo khoa học: Collective behavior in gene regulation: The cell is an oscillator, the cell cycle a developmental process

The finding of a genome-wide oscillation in transcription that gates cells into S phase and coordinates mitochondrial and metabolic functions has altered our understanding of how the cell cycle is timed and how stable cellular phenotypes are maintained. | MINIREVIEW Collective behavior in gene regulation The cell is an oscillator the cell cycle a developmental process Robert R. Klevecz1 Caroline M. Li1 Ian Marcus1 and Paul H. Frankel2 1 Department of Biology Beckman Research Institute Duarte CA USA 2 Department of Biostatistics City of Hope MedicalCenter Duarte CA USA Keywords attractor cell cycle genome-wide microarray oscillation phenotype stochastic SVD wavelets yeast Correspondence R. R. Klevecz Dynamic Systems Group Department of Biology Beckman Research Institute City of Hope MedicalCenter Duarte CA 91010 USA Fax 1 626 930 5366 Tel 1 626 301 8348 E-mail rklevecz@ Received 10 December 2007 revised 18 February 2008 accepted 12 March 2008 doi The finding of a genome-wide oscillation in transcription that gates cells into S phase and coordinates mitochondrial and metabolic functions has altered our understanding of how the cell cycle is timed and how stable cellular phenotypes are maintained. Here we present the evidence and arguments in support of the idea that everything oscillates and the rationale for viewing the cell as an attractor from which deterministic noise can be tuned by appropriate coupling among the many feedback loops or regu-lons that make up the transcriptional-respiratory attractor cycle. The existence of this attractor also explains many of the dynamic macroscopic properties of the cell cycle and appears to be the timekeeping oscillator in both cell cycles and circadian rhythms. The path taken by this primordial oscillator in the course of differentiation or drug response may involve period-doubling behavior. Evidence for a relatively high-frequency timekeeping oscillator in yeast and mammalian cells comes from expression array analysis and GC MS in the case of yeast and primarily from macroscopic measures of phase response to perturbation in the case of mammalian cells. Low-amplitude genome-wide oscillations a ubiquitous but often unrecognized attribute