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Indeed, such a network may subserve the formation of unicellular leaf hairs (trichomes) in the model plant <jats:italic>Arabidopsis thaliana<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In order to investigate the capacity of small gene regulatory networks to generate multiple equilibria, we present a chemical reaction network (CRN)-based modeling formalism and describe a number of methods for CRN analysis in a parameter-free context. These methods are compared and applied to a full set of one-component subnetworks, as well as a large random sample from 40,680 similarly constructed two-component subnetworks. We find that positive feedback and cooperativity mediated by transcription factor (TF) dimerization is a requirement for one-component subnetwork bistability. For subnetworks with two components, the presence of these processes increases the probability that a randomly sampled subnetwork will exhibit multiple equilibria, although we find several examples of bistable two-component subnetworks that do not involve cooperative TF-promoter binding. In the specific case of epidermal differentiation in <jats:italic>Arabidopsis<\/jats:italic>, dimerization of the GL3-GL1 complex and cooperative sequential binding of GL3-GL1 to the CPC promoter are each independently sufficient for bistability.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Computational methods utilizing CRN-specific theorems to rule out bistability in small gene regulatory networks are far superior to techniques generally applicable to deterministic ODE systems. Using these methods to conduct an unbiased survey of parameter-free deterministic models of small networks, and the <jats:italic>Arabidopsis<\/jats:italic> epidermal cell differentiation subnetwork in particular, we illustrate how future experimental research may be guided by network structure analysis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-3-96","type":"journal-article","created":{"date-parts":[[2009,9,22]],"date-time":"2009-09-22T06:13:52Z","timestamp":1253600032000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The capacity for multistability in small gene regulatory networks"],"prefix":"10.1186","volume":"3","author":[{"given":"Dan","family":"Siegal-Gaskins","sequence":"first","affiliation":[]},{"given":"Erich","family":"Grotewold","sequence":"additional","affiliation":[]},{"given":"Gregory D","family":"Smith","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2009,9,21]]},"reference":[{"issue":"5594","key":"364_CR1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1126\/science.1075090","volume":"298","author":"TI Lee","year":"2002","unstructured":"Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, Zeitlinger J, Jennings EG, Murray HL, Gordon DB, Ren B, Wyrick JJ, Tagne JB, Volkert TL, Fraenkel E, Gifford DK, Young RA: Transcriptional regulatory networks in Saccharomyces cerevisiae. 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