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Abstract

Drosophila embryogenesis is characterized by rapid transitions in gene activity, whereby crudely distributed gradients of regulatory proteins give way to precise on/off patterns of gene expression. To explore the underlying mechanisms, a partially automated, quantitative in situ hybridization method was used to visualize expression profiles of 14 developmental control genes in hundreds of embryos. These studies revealed two distinct patterns of gene activation: synchronous and stochastic. Synchronous genes display essentially uniform expression of nascent transcripts in all cells of an embryonic tissue, whereas stochastic genes display erratic patterns of de novo activation. RNA polymerase II is "pre-loaded" (stalled) in the promoter regions of synchronous genes, but not stochastic genes. Transcriptional synchrony might ensure the orderly deployment of the complex gene regulatory networks that control embryogenesis.

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Nature, nurture, or chance: stochastic gene expression and its consequences.

Arjun Raj, Alexander van Oudenaarden (2008)

Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.

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Physics of chemoreception.

H.C. Berg, E.M Purcell (1977)

Statistical fluctuations limit the precision with which a microorganism can, in a given time T, determine the concentration of a chemoattractant in the surrounding medium. The best a cell can do is to monitor continually the state of occupation of receptors distributed over its surface. For nearly optimum performance only a small fraction of the surface need be specifically adsorbing. The probability that a molecule that has collided with the cell will find a receptor is Ns/(Ns + pi a), if N receptors, each with a binding site of radius s, are evenly distributed over a cell of radius a. There is ample room for many indenpendent systems of specific receptors. The adsorption rate for molecules of moderate size cannot be significantly enhanced by motion of the cell or by stirring of the medium by the cell. The least fractional error attainable in the determination of a concentration c is approximately (TcaD) - 1/2, where D is diffusion constant of the attractant. The number of specific receptors needed to attain such precision is about a/s. Data on bacteriophage absorption, bacterial chemotaxis, and chemotaxis in a cellular slime mold are evaluated. The chemotactic sensitivity of Escherichia coli approaches that of the cell of optimum design.

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RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo.

Julia Zeitlinger, Alexander Stark, Manolis Kellis … (2007)

It is widely assumed that the key rate-limiting step in gene activation is the recruitment of RNA polymerase II (Pol II) to the core promoter. Although there are well-documented examples in which Pol II is recruited to a gene but stalls, a general role for Pol II stalling in development has not been established. We have carried out comprehensive Pol II chromatin immunoprecipitation microarray (ChIP-chip) assays in Drosophila embryos and identified three distinct Pol II binding behaviors: active (uniform binding across the entire transcription unit), no binding, and stalled (binding at the transcription start site). The notable feature of the approximately 10% genes that are stalled is that they are highly enriched for developmental control genes, which are either repressed or poised for activation during later stages of embryogenesis. We propose that Pol II stalling facilitates rapid temporal and spatial changes in gene activity during development.

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PubMed ID:: 19628867

PMC ID:: 4280267

DOI:: 10.1126/science.1173976

ScienceOpen disciplines: Chemistry

Keywords: Animals,Drosophila,genetics,Embryo, Nonmammalian,Gene Expression Regulation, Developmental,Genes, Insect,RNA Polymerase II,metabolism,Stochastic Processes,Transcriptional Activation

Synchronous and stochastic patterns of gene activation in the Drosophila embryo.

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A Sustainable Future

Most cited references 25

Nature, nurture, or chance: stochastic gene expression and its consequences.

Physics of chemoreception.

RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo.

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