Mechanism of life-long maintenance of neuron identity despite molecular fluctuations
| Autor: | Traets, Joleen Jh, Van Der Burght, Servaas N, Rademakers, Suzanne, Jansen, Gert, Van Zon, Jeroen S |
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| Přispěvatelé: | Cell biology, Traets, Joleen Jh [0000-0003-0505-9776], van der Burght, Servaas N [0000-0002-3272-3815], Jansen, Gert [0000-0002-7524-171X], van Zon, Jeroen S [0000-0002-6021-2924], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
bistability
stochastic gene expression QH301-705.5 Science gene regulatory network General Biochemistry Genetics and Molecular Biology developmental biology physics of living systems Animals neuronal cell fate chemotaxis Biology (General) Caenorhabditis elegans Caenorhabditis elegans Proteins Neurons General Immunology and Microbiology integumentary system General Neuroscience General Medicine molecular fluctuations C. elegans Medicine Research Article Transcription Factors |
| Zdroj: | eLife, 10:e66955. eLife Sciences Publications eLife, Vol 10 (2021) eLife |
| ISSN: | 2050-084X |
| Popis: | Cell 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. |
| Databáze: | OpenAIRE |
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