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 and Matthias Merkenschlager ()
Additional contact information
Irene Robles-Rebollo: Imperial College London
Sergi Cuartero: Imperial College London
Adria Canellas-Socias: Imperial College London
Sarah Wells: Imperial College London
Mohammad M. Karimi: Imperial College London
Elisabetta Mereu: The Barcelona Institute of Science and Technology (BIST)
Alexandra G. Chivu: Imperial College London
Holger Heyn: The Barcelona Institute of Science and Technology (BIST)
Chad Whilding: Imperial College London
Dirk Dormann: Imperial College London
Samuel Marguerat: Imperial College London
Inmaculada Rioja: GlaxoSmithKline Medicines Research Centre
Rab K. Prinjha: GlaxoSmithKline Medicines Research Centre
Michael P. H. Stumpf: Imperial College London
Amanda G. Fisher: Imperial College London
Matthias Merkenschlager: Imperial College London

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31192-9

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DOI: 10.1038/s41467-022-31192-9

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