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Transcriptional bursting in Drosophila development: Stochastic dynamics of eve stripe 2 expression

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  • David M Holloway
  • Alexander V Spirov

Abstract

Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first seen in the 7-stripe spatial expression patterns of the pair-rule genes, which regulate downstream genes determining specific segment identities. Regulation of pair-rule expression has been extensively studied for the even-skipped (eve) gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated the stochastic nature of this process, with ‘bursts’ in the number of RNA transcripts being made over time. We developed a stochastic model of the spatial and temporal expression of eve stripe 2 (binding by transcriptional activators (Bicoid and Hunchback proteins) and repressors (Giant and Krüppel proteins), transcriptional initiation and termination; with all rate parameters constrained by features of the experimental data) in order to analyze the noisy experimental time series and test hypotheses for how eve transcription is regulated. These include whether eve transcription is simply OFF or ON, with a single ON rate, or whether it proceeds by a more complex mechanism, with multiple ON rates. We find that both mechanisms can produce long (multi-minute) RNA bursts, but that the short-time (minute-to-minute) statistics of the data is indicative of eve being transcribed with at least two distinct ON rates, consistent with data on the joint activation of eve by Bicoid and Hunchback. We also predict distinct statistical signatures for cases in which eve is repressed (e.g. along the edges of the stripe) vs. cases in which activation is reduced (e.g. by mutagenesis of transcription factor binding sites). Fundamental developmental processes such as gene transcription are intrinsically noisy; our approach presents a new way to quantify and analyze time series data during developmental patterning in order to understand regulatory mechanisms and how they propagate noise and impact embryonic robustness.

Suggested Citation

  • David M Holloway & Alexander V Spirov, 2017. "Transcriptional bursting in Drosophila development: Stochastic dynamics of eve stripe 2 expression," PLOS ONE, Public Library of Science, vol. 12(4), pages 1-24, April.
  • Handle: RePEc:plo:pone00:0176228
    DOI: 10.1371/journal.pone.0176228
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    References listed on IDEAS

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    1. David M Holloway & Francisco J P Lopes & Luciano da Fontoura Costa & Bruno A N Travençolo & Nina Golyandina & Konstantin Usevich & Alexander V Spirov, 2011. "Gene Expression Noise in Spatial Patterning: hunchback Promoter Structure Affects Noise Amplitude and Distribution in Drosophila Segmentation," PLOS Computational Biology, Public Library of Science, vol. 7(2), pages 1-18, February.
    2. William J. Blake & Mads KÆrn & Charles R. Cantor & J. J. Collins, 2003. "Noise in eukaryotic gene expression," Nature, Nature, vol. 422(6932), pages 633-637, April.
    3. Johannes Jaeger & Svetlana Surkova & Maxim Blagov & Hilde Janssens & David Kosman & Konstantin N. Kozlov & Manu & Ekaterina Myasnikova & Carlos E. Vanario-Alonso & Maria Samsonova & David H. Sharp & J, 2004. "Dynamic control of positional information in the early Drosophila embryo," Nature, Nature, vol. 430(6997), pages 368-371, July.
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    1. Chen, Xiaoli & Wu, Fengyan & Duan, Jinqiao & Kurths, Jürgen & Li, Xiaofan, 2019. "Most probable dynamics of a genetic regulatory network under stable Lévy noise," Applied Mathematics and Computation, Elsevier, vol. 348(C), pages 425-436.

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