Enhancer Priming Enables Fast and Sustained Transcriptional Responses to Notch Signaling.
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Falo-Sanjuan, J., Lammers, N. C., Garcia, H. G., & Bray, S. (2019). Enhancer Priming Enables Fast and Sustained Transcriptional Responses to Notch Signaling.. Developmental cell, 50 (4), 411-425.e8. https://doi.org/10.1016/j.devcel.2019.07.002
Information from developmental signaling pathways must be accurately decoded to generate transcriptional outcomes. In the case of Notch, the intracellular domain (NICD) transduces the signal directly to the nucleus. How enhancers decipher NICD in the real time of developmental decisions is not known. Using the MS2/MCP system to visualize nascent transcripts in single cells in Drosophila embryos we reveal how two target enhancers read Notch activity to produce synchronized and sustained profiles of transcription. By manipulating the levels of NICD and altering specific motifs within the enhancers we uncover two key principles. First, increased NICD levels alter transcription by increasing duration rather than frequency of transcriptional bursts. Second, priming of enhancers by tissue-specific transcription factors is required for NICD to confer synchronized and sustained activity; in their absence, transcription is stochastic and bursty. The dynamic response of an individual enhancer to NICD thus differs depending on the cellular context.
Embryo, Nonmammalian, Animals, Animals, Genetically Modified, Drosophila melanogaster, Drosophila Proteins, Nuclear Proteins, Phosphoproteins, Transcription Factors, Signal Transduction, Transcription, Genetic, Gene Expression Regulation, Developmental, Binding Sites, Regulatory Sequences, Nucleic Acid, Embryonic Development, Receptors, Notch, Enhancer Elements, Genetic, Transcriptional Activation, Twist-Related Protein 1
Wellcome Trust (212207/Z/18/Z)
WELLCOME TRUST (109144/Z/15/Z)
External DOI: https://doi.org/10.1016/j.devcel.2019.07.002
This record's URL: https://www.repository.cam.ac.uk/handle/1810/294674
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/