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Mechanism of life-long maintenance of neuron identity despite molecular fluctuations.

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cam.depositDate2022-02-28
cam.issuedOnline2021-12-15
dc.contributor.authorTraets, Joleen Jh
dc.contributor.authorvan der Burght, Servaas N
dc.contributor.authorRademakers, Suzanne
dc.contributor.authorJansen, Gert
dc.contributor.authorvan Zon, Jeroen S
dc.contributor.orcidTraets, Joleen Jh [0000-0003-0505-9776]
dc.contributor.orcidvan der Burght, Servaas N [0000-0002-3272-3815]
dc.contributor.orcidJansen, Gert [0000-0002-7524-171X]
dc.contributor.orcidvan Zon, Jeroen S [0000-0002-6021-2924]
dc.date.accessioned2022-03-01T00:30:45Z
dc.date.available2022-03-01T00:30:45Z
dc.date.issued2021-12-15
dc.date.updated2022-02-28T14:06:09Z
dc.description.abstractCell fate is maintained over long timescales, yet molecular fluctuations can lead to spontaneous loss of this differentiated state. Our simulations identified a possible mechanism that explains life-long maintenance of ASE neuron fate in Caenorhabditis elegans by the terminal selector transcription factor CHE-1. Here, fluctuations in CHE-1 level are buffered by the reservoir of CHE-1 bound at its target promoters, which ensures continued che-1 expression by preferentially binding the che-1 promoter. We provide experimental evidence for this mechanism by showing that che-1 expression was resilient to induced transient CHE-1 depletion, while both expression of CHE-1 targets and ASE function were lost. We identified a 130 bp che-1 promoter fragment responsible for this resilience, with deletion of a homeodomain binding site in this fragment causing stochastic loss of ASE identity long after its determination. Because network architectures that support this mechanism are highly conserved in cell differentiation, it may explain stable cell fate maintenance in many systems.
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.81946
dc.identifier.eissn2050-084X
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334528
dc.language.isoeng
dc.publishereLife Sciences Publications, Ltd
dc.publisher.departmentWellcome Trust/Cancer Research Uk Gurdon Institute
dc.publisher.urlhttp://dx.doi.org/10.7554/elife.66955
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectC. elegans
dc.subjectbistability
dc.subjectchemotaxis
dc.subjectdevelopmental biology
dc.subjectgene regulatory network
dc.subjectmolecular fluctuations
dc.subjectneuronal cell fate
dc.subjectphysics of living systems
dc.subjectstochastic gene expression
dc.subjectAnimals
dc.subjectCaenorhabditis elegans
dc.subjectCaenorhabditis elegans Proteins
dc.subjectNeurons
dc.subjectTranscription Factors
dc.titleMechanism of life-long maintenance of neuron identity despite molecular fluctuations.
dc.typeArticle
dcterms.dateAccepted2021-12-14
prism.numberARTN e66955
prism.publicationDate2021
prism.publicationNameElife
prism.startingPagee66955
prism.volume10
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.7554/eLife.66955

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