Paused Pol II Coordinates Tissue Morphogenesis in the Drosophila Embryo

• Published in: Cell Vol. 153; no. 5; pp. 976 - 987
• Main Authors: Lagha, Mounia, Bothma, Jacques P., Esposito, Emilia, Ng, Samuel, Stefanik, Laura, Tsui, Chiahao, Johnston, Jeffrey, Chen, Kai, Gilmour, David S., Zeitlinger, Julia, Levine, Michael S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.05.2013; Elsevier
• Subjects: Animals; Base Sequence; cells; DNA-directed RNA polymerase; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila Proteins - metabolism; Embryo, Nonmammalian - metabolism; Gastrulation; gene activation; gene expression; Gene Expression Regulation, Developmental; Life Sciences; mammals; Models, Biological; Molecular Sequence Data; Morphogenesis; Promoter Regions, Genetic; RNA Polymerase II - metabolism; snails; stem cells; transcription (genetics); Transcription, Genetic
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2013.04.045

Paused RNA polymerase (Pol II) is a pervasive feature of Drosophila embryos and mammalian stem cells, but its role in development is uncertain. Here, we demonstrate that a spectrum of paused Pol II determines the “time to synchrony”—the time required to achieve coordinated gene expression across the cells of a tissue. To determine whether synchronous patterns of gene activation are significant in development, we manipulated the timing of snail expression, which controls the coordinated invagination of ∼1,000 mesoderm cells during gastrulation. Replacement of the strongly paused snail promoter with moderately paused or nonpaused promoters causes stochastic activation of snail expression and increased variability of mesoderm invagination. Computational modeling of the dorsal-ventral patterning network recapitulates these variable and bistable gastrulation profiles and emphasizes the importance of timing of gene activation in development. We conclude that paused Pol II and transcriptional synchrony are essential for coordinating cell behavior during morphogenesis. [Display omitted] •Minimal promoter sequences are sufficient to establish paused RNA polymerase•Levels of paused polymerase determine the timing of transcription•Stochastic activation of snail expression disrupts mesoderm invagination•Paused Pol II and transcriptional synchrony coordinate gastrulation Pausing of Pol II at the promoter of snail enables its synchronous expression across the cells of the embryo. Experimental expression of snail from a nonpaused or moderately paused promoter results in its stochastic activation, which disrupts invagination of the mesoderm during gastrulation.