Browsing by Subject "Genes, Helminth"
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Item Open Access Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression.(Mol Syst Biol, 2008) Yanai, Itai; Baugh, L Ryan; Smith, Jessica J; Roehrig, Casey; Shen-Orr, Shai S; Claggett, Julia M; Hill, Andrew A; Slonim, Donna K; Hunter, Craig PBiological 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.Item Open Access Pol II docking and pausing at growth and stress genes in C. elegans.(Cell Rep, 2014-02-13) Maxwell, Colin S; Kruesi, William S; Core, Leighton J; Kurhanewicz, Nicole; Waters, Colin T; Lewarch, Caitlin L; Antoshechkin, Igor; Lis, John T; Meyer, Barbara J; Baugh, L RyanFluctuations in nutrient availability profoundly impact gene expression. Previous work revealed postrecruitment regulation of RNA polymerase II (Pol II) during starvation and recovery in Caenorhabditis elegans, suggesting that promoter-proximal pausing promotes rapid response to feeding. To test this hypothesis, we measured Pol II elongation genome wide by two complementary approaches and analyzed elongation in conjunction with Pol II binding and expression. We confirmed bona fide pausing during starvation and also discovered Pol II docking. Pausing occurs at active stress-response genes that become downregulated in response to feeding. In contrast, "docked" Pol II accumulates without initiating upstream of inactive growth genes that become rapidly upregulated upon feeding. Beyond differences in function and expression, these two sets of genes have different core promoter motifs, suggesting alternative transcriptional machinery. Our work suggests that growth and stress genes are both regulated postrecruitment during starvation but at initiation and elongation, respectively, coordinating gene expression with nutrient availability.