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Activation of the Notch Signaling Pathway In Vivo Elicits Changes in CSL Nuclear Dynamics.

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Gomez-Lamarca, Maria J 
Falo-Sanjuan, Julia 
Stojnic, Robert 
Abdul Rehman, Sohaib 


A key feature of Notch signaling is that it directs immediate changes in transcription via the DNA-binding factor CSL, switching it from repression to activation. How Notch generates both a sensitive and accurate response-in the absence of any amplification step-remains to be elucidated. To address this question, we developed real-time analysis of CSL dynamics including single-molecule tracking in vivo. In Notch-OFF nuclei, a small proportion of CSL molecules transiently binds DNA, while in Notch-ON conditions CSL recruitment increases dramatically at target loci, where complexes have longer dwell times conferred by the Notch co-activator Mastermind. Surprisingly, recruitment of CSL-related corepressors also increases in Notch-ON conditions, revealing that Notch induces cooperative or "assisted" loading by promoting local increase in chromatin accessibility. Thus, in vivo Notch activity triggers changes in CSL dwell times and chromatin accessibility, which we propose confer sensitivity to small input changes and facilitate timely shut-down.



CSL, FRAP, Suppressor of Hairless, assisted loading, chromatin, live imaging, locus tag, notch signaling, nuclear dynamics, single-molecule tracking, Animals, Cell Nucleus, DNA, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Models, Molecular, Protein Binding, Receptors, Notch, Signal Transduction, Transcriptional Activation

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Dev Cell

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Elsevier BV
Medical Research Council (MR/L007177/1)
Medical Research Council (MR/K015850/1)
BBSRC (1502069)
Engineering and Physical Sciences Research Council (EP/R025398/1)
Wellcome Trust (099744/Z/12/Z)
Wellcome Trust (099130/Z/12/Z)
Engineering and Physical Sciences Research Council (EP/L015455/1)
Biotechnology and Biological Sciences Research Council (BB/J014540/1)