RRC ID 57362
Author Gomez-Lamarca MJ, Falo-Sanjuan J, Stojnic R, Abdul Rehman S, Muresan L, Jones ML, Pillidge Z, Cerda-Moya G, Yuan Z, Baloul S, Valenti P, Bystricky K, Payre F, O'Holleran K, Kovall R, Bray SJ.
Title Activation of the Notch Signaling Pathway In Vivo Elicits Changes in CSL Nuclear Dynamics.
Journal Dev Cell
Abstract 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.
Volume 44(5)
Pages 611-623.e7
Published 2018-3-12
DOI 10.1016/j.devcel.2018.01.020
PII S1534-5807(18)30055-8
PMID 29478922
PMC PMC5855320
MeSH Animals Cell Nucleus / genetics* Cell Nucleus / metabolism DNA / genetics DNA / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Drosophila melanogaster / metabolism* Models, Molecular Protein Binding Receptors, Notch / genetics Receptors, Notch / metabolism* Signal Transduction Transcriptional Activation
IF 9.19
Times Cited 15
Drosophila DGRC#101292 DGRC#115513