Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters

Irene Robles-Rebollo, Sergi Cuartero, Adria Canellas-Socias, Sarah Wells, Mohammad M. Karimi, Elisabetta Mereu, Alexandra G. Chivu, Holger Heyn, Chad Whilding, Dirk Dormann, Samuel Marguerat, Inmaculada Rioja, Rab K. Prinjha, Michael P.H. Stumpf, Amanda G. Fisher, Matthias Merkenschlager*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Innate immune responses rely on inducible gene expression programmes which, in contrast to steady-state transcription, are highly dependent on cohesin. Here we address transcriptional parameters underlying this cohesin-dependence by single-molecule RNA-FISH and single-cell RNA-sequencing. We show that inducible innate immune genes are regulated predominantly by an increase in the probability of active transcription, and that probabilities of enhancer and promoter transcription are coordinated. Cohesin has no major impact on the fraction of transcribed inducible enhancers, or the number of mature mRNAs produced per transcribing cell. Cohesin is, however, required for coupling the probabilities of enhancer and promoter transcription. Enhancer-promoter coupling may not be explained by spatial proximity alone, and at the model locus Il12b can be disrupted by selective inhibition of the cohesinopathy-associated BET bromodomain BD2. Our data identify discrete steps in enhancer-mediated inducible gene expression that differ in cohesin-dependence, and suggest that cohesin and BD2 may act on shared pathways.

Original languageEnglish
Article number4342
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022

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