Sequential recruitment and combinatorial assembling of multiprotein complexes in transcriptional activation.
In human cells, estrogenic signals induce cyclical association and dissociation of specific proteins with the DNA in order to activate transcription of estrogen-responsive genes. These oscillations can be modeled by assuming a large number of sequential reactions represented by linear kinetics with random kinetic rates. Application of the model to experimental data predicts robust binding sequences in which proteins associate with the DNA at several different phases of the oscillation. Our methods circumvent the need to derive detailed kinetic graphs, and are applicable to other oscillatory biological processes involving a large number of sequential steps.
Lemaire
Vincent
V
Centre for Nonlinear Dynamics, McGill University, Canada. lemaire@cnd.mcgill.ca
Lee
Chiu Fan
CF
Lei
Jinzhi
J
Métivier
Raphaël
R
Glass
Leon
L
D000818:Animals; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015533:Transcriptional Activation
D002843:Chromatin; D004268:DNA-Binding Proteins; D004967:Estrogens; D004958:Estradiol; D004247:DNA