Celebrating 10 years of our lab with a new preprint: www.biorxiv.org/content/10.1... How does enhancer location within a TAD control transcriptional bursts from a cognate promoter? Experiments by Jana Tünnermann and modelling by Gregory Roth - ThreadSky

lucagiorgetti.bsky.social • 62 days ago

Celebrating 10 years of our lab with a new preprint:
https://www.biorxiv.org/content/10.1101/2025.03.26.645410v1
How does enhancer location within a TAD control transcriptional bursts from a cognate promoter?
Experiments by Jana Tünnermann and modelling by Gregory Roth

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geneticsmike7.bsky.social•62 days ago

Very excited to read this, loved the 2022 paper!

obsessedwithsexdog.bsky.social•62 days ago

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lucagiorgetti.bsky.social•62 days ago

(2/n) We modified our enhancer mobilization assay (https://www.nature.com/articles/s41586-022-04570-y) to enable MS2-mediated visualization of active transcription sites when the SCR enhancer is hopped and reinserted into different random positions around an ectopic copy of the Sox2 promoter inside a ‘neutral’ TAD.

lucagiorgetti.bsky.social•62 days ago

(3/n) We show that enhancer position controls the promoter burst frequency, but not burst duration and size

lucagiorgetti.bsky.social•62 days ago

(4/n) When it is located close to the promoter, the enhancer drives more frequent bursts than when it is located far away, resulting in a more uniform transcriptional output. Thus enhancer location within a cis-regulatory landscape is a major determinant of how accurately a gene is transcribed!

lucagiorgetti.bsky.social•62 days ago

(5/n) We also observed that bursts occur in clusters, with inter-burst duration distributed across three timescales and correlated in time

lucagiorgetti.bsky.social•62 days ago

(6/n) This behavior cannot be described by previous models of promoter operation (either two- or multi-state models) that have a single regime of burst frequency. The simplest model that accounts for all our observations is a double-regime two-state model …

lucagiorgetti.bsky.social•62 days ago

(7/n) … in which the promoter stochastically switches between a ‘basal’ low burst-frequency regime and a high burst-frequency regime where clusters of bursts become more frequent

vjsanchez.bsky.social•59 days ago

Congrats Luca!

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