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dc.contributor.authorWurmser, Annabelle
dc.contributor.authorBasu, Srinjan
dc.date.accessioned2022-05-09T09:11:14Z
dc.date.available2022-05-09T09:11:14Z
dc.date.issued2022
dc.date.submitted2022-01-31
dc.identifier.issn2296-889X
dc.identifier.other867303
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336822
dc.description.abstractCis-regulatory elements such as enhancers can be located even a million base pairs away from their cognate promoter and yet modulate gene transcription. Indeed, the 3D organisation of chromatin enables the establishment of long-range enhancer-promoter communication. The observation of long-range enhancer-promoter chromatin loops at active genes originally led to a model in which enhancers and promoters form physical contacts between each other to control transcription. Yet, recent microscopy data has challenged this prevailing activity-by-contact model of enhancer-promoter communication in transcriptional activation. Live single-cell imaging approaches do not systematically reveal a correlation between enhancer-proximity and transcriptional activation. We therefore discuss the need to move from a static to a dynamic view of enhancer-promoter relationships. We highlight recent studies that not only reveal considerable chromatin movement in specific cell types, but suggest links between chromatin compaction, chromatin movement and transcription. We describe the interplay between enhancer-promoter proximity within the context of biomolecular condensates and the need to understand how condensate microenvironments influence the chromatin binding kinetics of proteins that bind at cis-regulatory elements to activate transcription. Finally, given the complex multi-scale interplay between regulatory proteins, enhancer-promoter proximity and movement, we propose the need to integrate information from complementary single-cell next-generation sequencing and live-cell imaging approaches to derive unified 3D theoretical models of enhancer-promoter communication that are ultimately predictive of transcriptional output and cell fate. In time, improved models will shed light on how tissues grow and diseases emerge.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectMolecular Biosciences
dc.subjectchromatin mobility
dc.subjectenhancer-promoter communication
dc.subjectenhancer-promoter interaction
dc.subjecttranscription
dc.subjectstem cell
dc.subjectcell fate and differentiation
dc.titleEnhancer-Promoter Communication: It's Not Just About Contact.
dc.typeOther
dc.date.updated2022-05-09T09:11:14Z
prism.publicationNameFront Mol Biosci
prism.volume9
dc.identifier.doi10.17863/CAM.84241
dcterms.dateAccepted2022-03-24
rioxxterms.versionofrecord10.3389/fmolb.2022.867303
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBasu, Srinjan [0000-0002-1080-979X]
dc.identifier.eissn2296-889X
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idMedical Research Council (MC_PC_17230)
cam.issuedOnline2022-04-19


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