Dynamics of Notch-Dependent Transcriptional Bursting in Its Native Context

Developmental Cell
ChangHwan LeeJudith Kimble

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.

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Citations

Dec 31, 2019·Development, Growth & Differentiation·Julia Falo-Sanjuan, Sarah J Bray
Jan 9, 2020·Science Signaling·Ralitsa R Madsen, Bart Vanhaesebroeck
Oct 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sarah Robinson-ThiewesJudith Kimble
Aug 6, 2019·Developmental Cell·Julia Falo-SanjuanSarah J Bray
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Jul 22, 2021·Molecular Systems Biology·Victor L BassKathryn Miller-Jensen
Aug 31, 2021·Clinical and Translational Medicine·Diane Catherine Wang, Xiangdong Wang

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