Nonequilibrium model of short-range repression in gene transcription regulation.

Transcription factors are proteins that regulate gene activity by activating or repressing gene transcription. A special class of transcriptional repressors operates via a short-range mechanism, making local DNA regions inaccessible to binding by activators, and thus providing an indirect repressive action on the target gene. This mechanism is commonly modeled assuming that repressors interact with DNA under thermodynamic equilibrium and neglecting some configurations of the gene regulatory region. We elaborate on a more general nonequilibrium model of short-range repression using the graph formalism for transitions between gene states, and we apply analytical calculations to compare it with the equilibrium model in terms of the repression strength and expression noise. In contrast to the equilibrium approach, the new model allows us to separate two basic mechanisms of short-range repression. The first mechanism is associated with the recruiting of factors that mediate chromatin condensation, and the second one concerns the blocking of factors that mediate chromatin loosening. The nonequilibrium model demonstrates better performance on previously published gene expression data obtained for transcription factors controlling Drosophila development, and furthermore it predicts that the first repression mechanism is the most favorable in this system. The presented approach can be scaled to larger gene networks and can be used to infer specific modes and parameters of transcriptional regulation from gene expression data.

[Modelling of Drosophila gap gene network under Bcd morphogen variation].

Expression patterns of segmentation genes are formed under the influence of maternal transcription factor gradients, which initiate spatially localized expression in the cascade of segmentation genes. Bcd is one of these activators. We have studied one model of regulation in the gap gene network by varying the concentration of this protein. We have shown that the known gap gene network topology is not sufficient to explain experimental data on the shifts exhibited by the hb anterior expression domain by change in Bcd concentration in the embryo. As the result of modeling with these experimental data taken into account, a new topology is obtained that determines the correct shifts of the hb expression domain. These results suggest that interactions among the three hb, Kr and gt genes are key regulatory factors for the valid behaviour of the hb expression pattern with Bcd concentration changes. This study made it possible to specify the limits of validity for phenomenological models of gene networks.