title: Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression.
abstract: Biological networks are inherently modular, yet little is known about how modules are assembled to enable coordinated and complex functions. We used RNAi and time series, whole-genome microarray analyses to systematically perturb and characterize components of a Caenorhabditis elegans lineage-specific transcriptional regulatory network. These data are supported by selected reporter gene analyses and comprehensive yeast one-hybrid and promoter sequence analyses. Based on these results, we define and characterize two modules composed of muscle- and epidermal-specifying transcription factors that function together within a single cell lineage to robustly specify multiple cell types. The expression of these two modules, although positively regulated by a common factor, is reliably segregated among daughter cells. Our analyses indicate that these modules repress each other, and we propose that this cross-inhibition coupled with their relative time of induction function to enhance the initial asymmetry in their expression patterns, thus leading to the observed invariant gene expression patterns and cell lineage. The coupling of asynchronous and topologically distinct modules may be a general principle of module assembly that functions to potentiate genetic switches.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Itai
authors.initials: I
authors.lastname: Yanai
authors.forename: L Ryan
authors.initials: LR
authors.lastname: Baugh
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Smith
authors.forename: Casey
authors.initials: C
authors.lastname: Roehrig
authors.forename: Shai S
authors.initials: SS
authors.lastname: Shen-Orr
authors.forename: Julia M
authors.initials: JM
authors.lastname: Claggett
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hill
authors.forename: Donna K
authors.initials: DK
authors.lastname: Slonim
authors.forename: Craig P
authors.initials: CP
authors.lastname: Hunter
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D019070:Cell Lineage; D004625:Embryo, Nonmammalian; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D017238:Genes, Helminth; D005809:Genes, Regulator; D017930:Genes, Reporter; D008954:Models, Biological; D009132:Muscles / Q000166:cytology / Q000196:embryology; D009154:Mutation; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C102175:MEX-3 protein, C elegans; D016601:RNA-Binding Proteins