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Dynamic modes of Notch transcription hubs conferring memory and stochastic activation revealed by live imaging the co-activator Mastermind.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

DeHaro-Arbona, F Javier  ORCID logo  https://orcid.org/0000-0002-2307-0859
Roussos, Charalambos 
Baloul, Sarah 
Townson, Jonathan 
Gómez Lamarca, María J  ORCID logo  https://orcid.org/0000-0003-3750-7959

Abstract

Developmental programming involves the accurate conversion of signalling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the co-activator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote the formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module. The composition of the hub is labile and persists after Notch withdrawal conferring a memory that enables rapid reformation. Surprisingly, only a third of Notch ON hubs progress to a state with nascent transcription, which correlates with polymerase II and core Mediator recruitment. This probability is increased by a second signal. The discovery that target-gene transcription is probabilistic has far-reaching implications because it implies that stochastic differences in Notch pathway output can arise downstream of receptor activation.

Description

Keywords

D. melanogaster, Mastermind, Notch signalling, chromosomes, developmental biology, gene expression, live imaging, mediator complex, transcription, Receptors, Notch, Animals, Transcription, Genetic, Transcription Factors, Drosophila Proteins, Signal Transduction, Drosophila melanogaster, Stochastic Processes, Cell Nucleus

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Wellcome Trust (212207/Z/18/Z)
MRC (MR/T014156/1)