Direct observation of Notch signaling–induced transcription hubs mediating gene-expression responses

TL;DR

The study shows that Notch signaling creates transcription hubs that help cells respond to signals by controlling gene expression.

Contribution

The paper provides direct evidence that Notch signaling induces transcription hubs that influence gene-expression responses.

Findings

Notch signaling leads to the formation of transcription hubs containing the coactivator Mastermind.

Transcription hub formation precedes and correlates with gene transcription dynamics.

Altering signaling levels affects both hub intensity and transcription profiles.

Abstract

Developmental decisions rely on cells making accurate transcriptional responses to signals they receive, as with Notch pathway activity. Local condensates or transcription factor hubs are a proposed mechanism for facilitating gene activation by nuclear complexes. To investigate their importance in endogenous Notch signaling, we deployed multicolor live imaging to measure Notch transcription-complex enrichment at a target gene locus in combination with the transcription dynamics. The coactivator Mastermind (Mam) was present in signaling-dependent nuclear foci during Notch active developmental stages. Tracking these highly dynamic Mam hubs together with transcription in the same nucleus revealed that their appearance precedes and correlates with the profile of transcription and becomes stabilized if transcription is inhibited. Manipulations to signaling levels had concordant effects on hub intensities and transcription profiles, altering their probability and amplitude. Together, the results argue that signaling induces the formation of transcription hubs whose properties are instrumental in the quantitative gene-expression response to Notch activation.

Multicolor live imaging reveals Notch transcription-complex enrichment at a gene locus, which precedes and informs transcription.

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