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Activation of the Notch Signaling Pathway In Vivo Elicits Changes in CSL Nuclear Dynamics
Maria J Gomez-Lamarca1, Julia Falo-Sanjuan1, Robert Stojnic1
1Department of Physiology Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Developmental Cell
|February 27, 2018
Summary
Notch signaling rapidly alters gene transcription by changing the DNA binding of CSL proteins. This study reveals how Notch ensures sensitive and accurate responses through dynamic CSL interactions and chromatin accessibility.
Area of Science:
- Cellular biology
- Molecular biology
- Genetics
Background:
- Notch signaling is crucial for immediate transcriptional changes mediated by the DNA-binding factor CSL.
- The mechanisms underlying Notch's sensitive and accurate response, especially without amplification, are not fully understood.
Purpose of the Study:
- To investigate the real-time dynamics of CSL (CBF1/RBPJ-associated factor) in vivo during Notch signaling.
- To elucidate how Notch signaling achieves sensitivity and accuracy in transcriptional regulation.
Main Methods:
- Developed real-time analysis techniques for CSL dynamics.
- Employed single-molecule tracking in vivo to observe CSL behavior.
Main Results:
- In Notch-OFF states, CSL exhibits transient DNA binding.
- Notch-ON conditions significantly increase CSL recruitment to target loci with longer dwell times, facilitated by the Mastermind co-activator.
- CSL corepressor recruitment also increases, indicating Notch promotes cooperative loading via enhanced chromatin accessibility.
Conclusions:
- Notch signaling dynamically alters CSL dwell times and chromatin accessibility in vivo.
- These mechanisms likely confer sensitivity to minor input variations and enable efficient signal termination.
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