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.

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Citation

Published Version (Please cite this version)

10.1038/msb.2008.6

Publication Info

Yanai, Itai, L Ryan Baugh, Jessica J Smith, Casey Roehrig, Shai S Shen-Orr, Julia M Claggett, Andrew A Hill, Donna K Slonim, et al. (2008). Pairing of competitive and topologically distinct regulatory modules enhances patterned gene expression. Mol Syst Biol, 4. p. 163. 10.1038/msb.2008.6 Retrieved from https://hdl.handle.net/10161/13730.

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Scholars@Duke

Baugh

L. Ryan Baugh

Professor of Biology

The Baugh Lab is interested in phenotypic plasticity and physiological adaptation to variable environmental conditions. We are using the roundworm C. elegans to understand how animals adapt to starvation using primarily genetic and genomic approaches. We are studying how development is governed by nutrient availability, how animals survive starvation, and the long-term consequences of starvation including adult disease and transgenerational epigenetic inheritance.


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