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ABSTRACT: Transcription is an essential step in gene expression and its understanding has been one of the major interests in molecular and cellular biology. By precisely tuning gene expression, transcriptional regulation determines the molecular machinery for developmental plasticity, homeostasis and adaptation. In this review, we transmit the main ideas or concepts behind regulation by transcription factors and give just enough examples to sustain these main ideas, thus avoiding a classical ennumeration of facts. We review recent concepts and developments: cis elements and trans regulatory factors, chromosome organization and structure, transcriptional regulatory networks (TRNs) and transcriptomics. We also summarize new important discoveries that will probably affect the direction of research in gene regulation: epigenetics and stochasticity in transcriptional regulation, synthetic circuits and plasticity and evolution of TRNs. Many of the new discoveries in gene regulation are not extensively tested with wetlab approaches. Consequently, we review this broad area in Inference of TRNs and Dynamical Models of TRNs. Finally, we have stepped backwards to trace the origins of these modern concepts, synthesizing their history in a timeline schema.
FEMS Microbiology Reviews 02/2009; 33(1):133-51. · 10.96 Impact Factor
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ABSTRACT: The coordinated expression of the different genes in an organism is essential to sustain functionality under the random external perturbations to which the organism might be subjected. To cope with such external variability, the global dynamics of the genetic network must possess two central properties. (a) It must be robust enough as to guarantee stability under a broad range of external conditions, and (b) it must be flexible enough to recognize and integrate specific external signals that may help the organism to change and adapt to different environments. This compromise between robustness and adaptability has been observed in dynamical systems operating at the brink of a phase transition between order and chaos. Such systems are termed critical. Thus, criticality, a precise, measurable, and well characterized property of dynamical systems, makes it possible for robustness and adaptability to coexist in living organisms. In this work we investigate the dynamical properties of the gene transcription networks reported for S. cerevisiae, E. coli, and B. subtilis, as well as the network of segment polarity genes of D. melanogaster, and the network of flower development of A. thaliana. We use hundreds of microarray experiments to infer the nature of the regulatory interactions among genes, and implement these data into the Boolean models of the genetic networks. Our results show that, to the best of the current experimental data available, the five networks under study indeed operate close to criticality. The generality of this result suggests that criticality at the genetic level might constitute a fundamental evolutionary mechanism that generates the great diversity of dynamically robust living forms that we observe around us.
PLoS ONE 02/2008; 3(6):e2456. · 4.09 Impact Factor
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SEB experimental biology series. 02/2008; 61:113-39.
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ABSTRACT: Living organisms are robust to a great variety of genetic changes. Gene regulation networks and metabolic pathways self-organize and reaccommodate to make the organism perform with stability and reliability under many point mutations, gene duplications and gene deletions. At the same time, living organisms are evolvable, which means that these kind of genetic perturbations can eventually make the organism acquire new functions and adapt to new environments. It is still an open problem to determine how robustness and evolvability blend together at the genetic level to produce stable organisms that yet can change and evolve. Here we address this problem by studying the robustness and evolvability of the attractor landscape of genetic regulatory network models under the process of gene duplication followed by divergence. We show that an intrinsic property of this kind of networks is that, after the divergence of the parent and duplicate genes, with a high probability the previous phenotypes, encoded in the attractor landscape of the network, are preserved and new ones might appear. The above is true in a variety of network topologies and even for the case of extreme divergence in which the duplicate gene bears almost no relation with its parent. Our results indicate that networks operating close to the so-called "critical regime" exhibit the maximum robustness and evolvability simultaneously.
Journal of Theoretical Biology 05/2007; 245(3):433-48. · 2.21 Impact Factor
