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Dev Cell. 2019 Jul 24. pii: S1534-5807(19)30571-4. doi: 10.1016/j.devcel.2019.07.001. [Epub ahead of print]

Dynamics of Notch-Dependent Transcriptional Bursting in Its Native Context.

Author information

1
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
2
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Present address: David H. Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: jekimble@wisc.edu.

Abstract

Transcription is well known to be inherently stochastic and episodic, but the regulation of transcriptional dynamics is not well understood. Here, we analyze how Notch signaling modulates transcriptional bursting during animal development. Our focus is Notch regulation of transcription in germline stem cells of the nematode C. elegans. Using the MS2 system to visualize nascent transcripts and live imaging to record dynamics, we analyze bursting as a function of position within the intact animal. We find that Notch-dependent transcriptional activation is indeed "bursty"; that wild-type Notch modulates burst duration (ON-time) rather than duration of pauses between bursts (OFF-time) or mean burst intensity; and that a mutant Notch receptor, which is compromised for assembly into the Notch transcription factor complex, primarily modifies burst size (duration × intensity). These analyses thus visualize the effect of a canonical signaling pathway on metazoan transcriptional bursting in its native context.

KEYWORDS:

C. elegans germline; MS2 system; Notch signaling; burst duration; gradient; live imaging; stem cells; stochasticity; sygl-1; transcriptional bursting

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