title: Response delays and the structure of transcription networks.
abstract: Sensory transcription networks generally control rapid and reversible gene expression responses to external stimuli. Developmental transcription networks carry out slow and irreversible temporal programs of gene expression during development. It is important to understand the design principles that underlie the structure of sensory and developmental transcription networks. Cascades, which are chains of regulatory reactions, are a basic structural element of transcription networks. When comparing databases of sensory and developmental transcription networks, a striking difference is found in the distribution of cascade lengths. Here, we suggest that delay times in the responses of the network present a design constraint that influences the network architecture. We experimentally studied the response times in simple cascades constructed of well-characterized repressors in Escherichia coli. Accurate kinetics at high temporal resolution was measured using green fluorescent protein (GFP) reporters. We find that transcription cascades can show long delays of about one cell-cycle time per cascade step. Mathematical analysis suggests that such a delay is characteristic of cascades that are designed to minimize the response times for both turning-on and turning-off gene expression. The need to achieve rapid reversible responses in sensory transcription networks may help explain the finding that long cascades are very rare in databases of E.coli and Saccharomyces cerevisiae sensory transcription networks. In contrast, long cascades are common in developmental transcription networks from sea urchin and from Drosophila melanogaster. Response delay constraints are likely to be less important for developmental networks, since they control irreversible processes on the timescale of cell-cycles. This study highlights a fundamental difference between the architecture of sensory and developmental transcription networks.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, 76100, Rehovot, Israel.
authors.forename: Nitzan
authors.initials: N
authors.lastname: Rosenfeld
authors.forename: Uri
authors.initials: U
authors.lastname: Alon
mesh_terms: D000465:Algorithms; D000818:Animals; D002453:Cell Cycle; D030541:Databases, Genetic; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000737:chemistry / Q000378:metabolism; D008433:Mathematics; D008958:Models, Molecular; D010957:Plasmids; D018085:Regulon; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012617:Sea Urchins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: D008164:Luminescent Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins