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Enhancer Priming Enables Fast and Sustained Transcriptional Responses to Notch Signaling.

Accepted version
Peer-reviewed

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Type

Article

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Authors

Falo-Sanjuan, Julia 
Lammers, Nicholas C 
Garcia, Hernan G 
Bray, Sarah J 

Abstract

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.

Description

Keywords

Drosophila, Notch signaling, burst duration, enhancer, enhancer priming, live imaging, transcriptional bursting, Animals, Animals, Genetically Modified, Binding Sites, Drosophila Proteins, Drosophila melanogaster, Embryo, Nonmammalian, Embryonic Development, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Nuclear Proteins, Phosphoproteins, Receptors, Notch, Regulatory Sequences, Nucleic Acid, Signal Transduction, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Twist-Related Protein 1

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

50

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (212207/Z/18/Z)
Medical Research Council (MR/L007177/1)
Wellcome Trust (109144/Z/15/Z)
Wellcome Trust