O'Neill, Patrick K.Forder, RobertErill, Ivan2018-10-012018-10-012014-05-01Patrick K. O'Neill, Robert Forder, Ivan Erill, Informational Requirements for Transcriptional Regulation, Journal of Computational Biology, Volume 21(5): 373–384, 2014, doi: 10.1089/cmb.2014.003210.1089/cmb.2014.0032http://hdl.handle.net/11603/11416Transcription factors (TFs) regulate transcription by binding to specific sites in promoter regions. Information theory provides a useful mathematical framework to analyze the binding motifs associated with TFs but imposes several assumptions that limit their applicability to specific regulatory scenarios. Explicit simulations of the co-evolution of TFs and their binding motifs allow the study of the evolution of regulatory networks with a high degree of realism. In this work we analyze the impact of differential regulatory demands on the information content of TF-binding motifs by means of evolutionary simulations. We generalize a predictive index based on information theory, and we validate its applicability to regulatory scenarios in which the TF binds significantly to the genomic background. Our results show a logarithmic dependence of the evolved information content on the occupancy of target sites and indicate that TFs may actively exploit pseudo-sites to modulate their occupancy of target sites. In regulatory networks with differentially regulated targets, we observe that information content in TF-binding motifs is dictated primarily by the fraction of total probability mass that the TF assigns to its target sites, and we provide a predictive index to estimate the amount of information associated with arbitrarily complex regulatory systems. We observe that complex regulatory patterns can exert additional demands on evolved information content, but, given a total occupancy for target sites, we do not find conclusive evidence that this effect is because of the range of required binding affinities.12 pagesen-USThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.binding sitesevolutionevolutionary simulationin silico evolutioninformation contentregulationtranscription factortranscription networksUMBC High Performance Computing Facility (HPCF)Text