Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters
Robles-Rebollo, Irene (Imperial College London)
Cuartero, Sergi (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Canellas-Socias, Adrià (Institut de Recerca Biomèdica)
Wells, Sarah (Imperial College London)
Karimi, Mohammad M (King's College London)
Mereu, Elisabetta (Institut de Ciència i Tecnologia de Barcelona. Institut de Recerca en Biomedicina)
Chivu, Alexandra G (Cornell University)
Heyn, Holger (Institut de Ciència i Tecnologia de Barcelona. Institut de Recerca en Biomedicina)
Whilding, Chad (Imperial College London)
Dormann, Dirk (Imperial College London)
Marguerat, Samuel (Imperial College London)
Rioja, Inmaculada (GlaxoSmithKline Medicines Research Centre (Regne Unit))
Prinjha, Rab K (GlaxoSmithKline Medicines Research Centre (Regen Unit))
Stumpf, Michael P H (University of Melbourne)
Fisher, Amanda G (Imperial College London)
Merkenschlager, Mattihas (Imperial College London)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cell Cycle Proteins ; Chromosomal Proteins, Non-Histone ; Enhancer Elements, Genetic ; Probability ; RNA
Publicado en:	Nature communications, Vol. 13 Núm. 1 (december 2022) , p. 4342, ISSN 2041-1723

DOI: 10.1038/s41467-022-31192-9
PMID: 35896525

16 p, 4.9 MB

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