Search

The Saccharomyces cerevisiae [PSI+] factor is a non-Mendelian trait that causes suppression of nonsense mutations in the yeast. To elucidate the conversion of amyloid fibril from its native state, the prion-like mechanism behind the propagation of the [PSI+] factor was investigated. The [PSI+] system was used to define sequence requirements for the in vivo formation and propagation of Sup35p amyloids. Results revealed a critical role for glutamine and asparagine residues in the amyloid state's stability. In addition, insights were made about the prion hypothesis.

Summary Computational models of enhancer function generally assume that transcription factors (TFs) exert their regulatory effects independently, modeling an enhancer as a “bag of sites.” These models fail on endogenous loci that harbor multiple enhancers, and a “two-tier” model appears better suited: in each enhancer TFs work independently, and the total expression is a weighted sum of their expression readouts. Here, we test these two opposing views on how cis -regulatory information is integrated. We fused two Drosophila blastoderm enhancers, measured their readouts, and applied the above two models to these data. The two-tier mechanism better fits these readouts, suggesting that these fused enhancers comprise multiple independent modules, despite having sequence characteristics typical of single enhancers. We show that short-range TF-TF interactions are not sufficient to designate such modules, suggesting unknown underlying mechanisms. Our results underscore that mechanisms of how modules are defined and how their outputs are combined remain to be elucidated. [ABSTRACT FROM AUTHOR]

Summary Many developmental genes are controlled by shadow enhancers—pairs of enhancers that drive overlapping expression patterns. We hypothesized that compensatory evolution can maintain the total expression of a gene, while individual shadow enhancers diverge between species. To test this hypothesis, we analyzed expression driven by orthologous pairs of shadow enhancers from Drosophila melanogaster , Drosophila yakuba , and Drosophila pseudoobscura that control expression of Krüppel , a transcription factor that patterns the anterior-posterior axis of blastoderm embryos. We found that the expression driven by the pair of enhancers is conserved between these three species, but expression levels driven by the individual enhancers are not. Using sequence analysis and experimental perturbation, we show that each shadow enhancer is regulated by different transcription factors. These results support the hypothesis that compensatory evolution can occur between shadow enhancers, which has implications for mechanistic and evolutionary studies of gene regulation. [ABSTRACT FROM AUTHOR]

Quantitative models of developmental processes can provide insights at multiple scales. Ultimately, models may be particularly informative for key questions about network level behavior during development such as how does the system respond to environmental perturbation, or operate reliably in different genetic backgrounds? The transcriptional networks that pattern the Drosophila embryo have been the subject of numerous quantitative experimental studies coupled to modeling frameworks in recent years. In this review, we describe three studies that consider these networks at different levels of molecular detail and therefore result in different types of insights. We also discuss other developmental transcriptional networks operating in Drosophila, with the goal of highlighting what additional insights they may provide. [Copyright &y& Elsevier]

Summary Transcription of developmental genes is controlled by multiple enhancers. Frequently, more than one enhancer can activate transcription from the same promoter in the same cells. How is regulatory information from multiple enhancers combined to determine the overall expression output? We measure nascent transcription driven by a pair of shadow enhancers, each enhancer of the pair separately, and each duplicated, using live imaging in Drosophila embryos. This set of constructs allows us to quantify the input-output function describing signal integration by two enhancers. We show that signal integration performed by these shadow enhancers and duplications varies across the expression pattern, implying that how their activities are combined depends on the transcriptional regulators bound to the enhancers in different parts of the embryo. Characterizing signal integration by multiple enhancers is a critical step in developing conceptual and computational models of gene expression at the locus level, where multiple enhancers control transcription together. Graphical Abstract Highlights • Measured dynamic expression from Krüppel shadow enhancers and their duplicates • The input-output function of the pairs depends on the position in the embryo • The input-output function of the shadow pair depends on the enhancers' relative positions • Competition between enhancers to activate the promoter cannot fully explain these data Scholes et al. examine how shadow enhancers and enhancer duplications drive expression from a single promoter. They show that "signal integration" varies across the expression pattern, implying that how enhancers' activities combine depends on the transcriptional regulators they bind in different parts of the embryo. [ABSTRACT FROM AUTHOR]