Integrating analog and digital modes of gene expression at Arabidopsis FLC
Quantitative gene regulation at the cell population level can be achieved by two fundamentally different modes of regulation at individual gene copies. A ‘digital’ mode involves binary ON/OFF expression states, with population-level variation arising from the proportion of gene copies in each state,...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79743 |
| _version_ | 1827898152180514816 |
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| author | Rea L Antoniou-Kourounioti Anis Meschichi Svenja Reeck Scott Berry Govind Menon Yusheng Zhao John Fozard Terri Holmes Lihua Zhao Huamei Wang Matthew Hartley Caroline Dean Stefanie Rosa Martin Howard |
| author_facet | Rea L Antoniou-Kourounioti Anis Meschichi Svenja Reeck Scott Berry Govind Menon Yusheng Zhao John Fozard Terri Holmes Lihua Zhao Huamei Wang Matthew Hartley Caroline Dean Stefanie Rosa Martin Howard |
| author_sort | Rea L Antoniou-Kourounioti |
| collection | DOAJ |
| description | Quantitative gene regulation at the cell population level can be achieved by two fundamentally different modes of regulation at individual gene copies. A ‘digital’ mode involves binary ON/OFF expression states, with population-level variation arising from the proportion of gene copies in each state, while an ‘analog’ mode involves graded expression levels at each gene copy. At the Arabidopsis floral repressor FLOWERING LOCUS C (FLC), ‘digital’ Polycomb silencing is known to facilitate quantitative epigenetic memory in response to cold. However, whether FLC regulation before cold involves analog or digital modes is unknown. Using quantitative fluorescent imaging of FLC mRNA and protein, together with mathematical modeling, we find that FLC expression before cold is regulated by both analog and digital modes. We observe a temporal separation between the two modes, with analog preceding digital. The analog mode can maintain intermediate expression levels at individual FLC gene copies, before subsequent digital silencing, consistent with the copies switching OFF stochastically and heritably without cold. This switch leads to a slow reduction in FLC expression at the cell population level. These data present a new paradigm for gradual repression, elucidating how analog transcriptional and digital epigenetic memory pathways can be integrated. |
| first_indexed | 2024-03-12T23:00:06Z |
| format | Article |
| id | doaj.art-b98106c04e584ea7ad9eaee38aee9b16 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-12T23:00:06Z |
| publishDate | 2023-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b98106c04e584ea7ad9eaee38aee9b162023-07-19T14:32:17ZengeLife Sciences Publications LtdeLife2050-084X2023-07-011210.7554/eLife.79743Integrating analog and digital modes of gene expression at Arabidopsis FLCRea L Antoniou-Kourounioti0https://orcid.org/0000-0001-5226-521XAnis Meschichi1https://orcid.org/0000-0001-8946-6023Svenja Reeck2https://orcid.org/0000-0002-6362-5310Scott Berry3https://orcid.org/0000-0002-1838-4976Govind Menon4https://orcid.org/0000-0002-1028-5463Yusheng Zhao5https://orcid.org/0000-0002-5893-504XJohn Fozard6https://orcid.org/0000-0001-9181-8083Terri Holmes7https://orcid.org/0000-0002-8480-0755Lihua Zhao8https://orcid.org/0000-0002-1758-9873Huamei Wang9Matthew Hartley10https://orcid.org/0000-0001-6178-2884Caroline Dean11https://orcid.org/0000-0002-6555-3525Stefanie Rosa12https://orcid.org/0000-0002-8100-1253Martin Howard13https://orcid.org/0000-0001-7670-0781Department of Computational and Systems Biology, John Innes Centre, Norwich, United Kingdom; School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomSwedish University of Agricultural Sciences, Plant Biology Department, Uppsala, SwedenDepartment of Cell and Developmental Biology, John Innes Centre, Norwich, United KingdomEMBL Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, AustraliaDepartment of Computational and Systems Biology, John Innes Centre, Norwich, United KingdomState Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, ChinaDepartment of Computational and Systems Biology, John Innes Centre, Norwich, United KingdomFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich, United KingdomSwedish University of Agricultural Sciences, Plant Biology Department, Uppsala, SwedenCollege of Life Sciences, Wuhan University, Wuhan, ChinaEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, United KingdomDepartment of Cell and Developmental Biology, John Innes Centre, Norwich, United KingdomSwedish University of Agricultural Sciences, Plant Biology Department, Uppsala, SwedenDepartment of Computational and Systems Biology, John Innes Centre, Norwich, United KingdomQuantitative gene regulation at the cell population level can be achieved by two fundamentally different modes of regulation at individual gene copies. A ‘digital’ mode involves binary ON/OFF expression states, with population-level variation arising from the proportion of gene copies in each state, while an ‘analog’ mode involves graded expression levels at each gene copy. At the Arabidopsis floral repressor FLOWERING LOCUS C (FLC), ‘digital’ Polycomb silencing is known to facilitate quantitative epigenetic memory in response to cold. However, whether FLC regulation before cold involves analog or digital modes is unknown. Using quantitative fluorescent imaging of FLC mRNA and protein, together with mathematical modeling, we find that FLC expression before cold is regulated by both analog and digital modes. We observe a temporal separation between the two modes, with analog preceding digital. The analog mode can maintain intermediate expression levels at individual FLC gene copies, before subsequent digital silencing, consistent with the copies switching OFF stochastically and heritably without cold. This switch leads to a slow reduction in FLC expression at the cell population level. These data present a new paradigm for gradual repression, elucidating how analog transcriptional and digital epigenetic memory pathways can be integrated.https://elifesciences.org/articles/79743quantitative gene expressionSingle molecule RNA FISHFLCmathematical modeling |
| spellingShingle | Rea L Antoniou-Kourounioti Anis Meschichi Svenja Reeck Scott Berry Govind Menon Yusheng Zhao John Fozard Terri Holmes Lihua Zhao Huamei Wang Matthew Hartley Caroline Dean Stefanie Rosa Martin Howard Integrating analog and digital modes of gene expression at Arabidopsis FLC eLife quantitative gene expression Single molecule RNA FISH FLC mathematical modeling |
| title | Integrating analog and digital modes of gene expression at Arabidopsis FLC |
| title_full | Integrating analog and digital modes of gene expression at Arabidopsis FLC |
| title_fullStr | Integrating analog and digital modes of gene expression at Arabidopsis FLC |
| title_full_unstemmed | Integrating analog and digital modes of gene expression at Arabidopsis FLC |
| title_short | Integrating analog and digital modes of gene expression at Arabidopsis FLC |
| title_sort | integrating analog and digital modes of gene expression at arabidopsis flc |
| topic | quantitative gene expression Single molecule RNA FISH FLC mathematical modeling |
| url | https://elifesciences.org/articles/79743 |
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