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Cell. 2018 Oct 18;175(3):835-847.e25. doi: 10.1016/j.cell.2018.09.056.

Diverse Spatial Expression Patterns Emerge from Unified Kinetics of Transcriptional Bursting.

Author information

1
Joseph Henry Laboratories of Physics and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
2
Department of Molecular Biology and Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Joseph Henry Laboratories of Physics and the Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Developmental and Stem Cell Biology, Institut Pasteur, 75015 Paris, France. Electronic address: tg2@princeton.edu.

Abstract

How transcriptional bursting relates to gene regulation is a central question that has persisted for more than a decade. Here, we measure nascent transcriptional activity in early Drosophila embryos and characterize the variability in absolute activity levels across expression boundaries. We demonstrate that boundary formation follows a common transcription principle: a single control parameter determines the distribution of transcriptional activity, regardless of gene identity, boundary position, or enhancer-promoter architecture. We infer the underlying bursting kinetics and identify the key regulatory parameter as the fraction of time a gene is in a transcriptionally active state. Unexpectedly, both the rate of polymerase initiation and the switching rates are tightly constrained across all expression levels, predicting synchronous patterning outcomes at all positions in the embryo. These results point to a shared simplicity underlying the apparently complex transcriptional processes of early embryonic patterning and indicate a path to general rules in transcriptional regulation.

KEYWORDS:

Bayesian inference; Drosophila gap genes; embryonic development; pattern formation; single-molecule imaging; telegraph model; transcriptional kinetics

PMID:
30340044
DOI:
10.1016/j.cell.2018.09.056

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