A unified-field theory of genome organization and gene regulation
Summary: Our aim is to predict how often genic and non-genic promoters fire within a cell. We first review a parsimonious pan-genomic model for genome organization and gene regulation, where transcription rate is determined by proximity in 3D space of promoters to clusters containing appropriate fac...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422402443X |
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| author | Giuseppe Negro Massimiliano Semeraro Peter R. Cook Davide Marenduzzo |
| author_facet | Giuseppe Negro Massimiliano Semeraro Peter R. Cook Davide Marenduzzo |
| author_sort | Giuseppe Negro |
| collection | DOAJ |
| description | Summary: Our aim is to predict how often genic and non-genic promoters fire within a cell. We first review a parsimonious pan-genomic model for genome organization and gene regulation, where transcription rate is determined by proximity in 3D space of promoters to clusters containing appropriate factors and RNA polymerases. This model reconciles conflicting results indicating that regulatory mammalian networks are both simple (as over-expressing just 4 transcription factors switches cell state) and complex (as genome-wide association studies show phenotypes like cell type are determined by thousands of loci rarely encoding such factors). We then present 3D polymer simulations, and a proximity formula based on our biological model that enables prediction of transcriptional activities of all promoters in three human cell types. This simple fitting-free formula contains just one variable (distance on the genetic map to the nearest active promoter), and we suggest it can in principle be applied to any organism. |
| format | Article |
| id | doaj-art-fb1829e5ebdb4f8d9123af618cfe3fff |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-fb1829e5ebdb4f8d9123af618cfe3fff2025-08-20T02:35:05ZengElsevieriScience2589-00422024-12-01271211121810.1016/j.isci.2024.111218A unified-field theory of genome organization and gene regulationGiuseppe Negro0Massimiliano Semeraro1Peter R. Cook2Davide Marenduzzo3SUPA, School of Physics, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK; Dipartimento Interateneo di Fisica, Università degli Studi di Bari and INFN, Sezione di Bari, Via Amendola 173, I-70126 Bari, ItalyDipartimento Interateneo di Fisica, Università degli Studi di Bari and INFN, Sezione di Bari, Via Amendola 173, I-70126 Bari, ItalySir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Corresponding authorSUPA, School of Physics, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK; Corresponding authorSummary: Our aim is to predict how often genic and non-genic promoters fire within a cell. We first review a parsimonious pan-genomic model for genome organization and gene regulation, where transcription rate is determined by proximity in 3D space of promoters to clusters containing appropriate factors and RNA polymerases. This model reconciles conflicting results indicating that regulatory mammalian networks are both simple (as over-expressing just 4 transcription factors switches cell state) and complex (as genome-wide association studies show phenotypes like cell type are determined by thousands of loci rarely encoding such factors). We then present 3D polymer simulations, and a proximity formula based on our biological model that enables prediction of transcriptional activities of all promoters in three human cell types. This simple fitting-free formula contains just one variable (distance on the genetic map to the nearest active promoter), and we suggest it can in principle be applied to any organism.http://www.sciencedirect.com/science/article/pii/S258900422402443XNatural sciencesBiological sciencesSystems biologyData processing in systems biology |
| spellingShingle | Giuseppe Negro Massimiliano Semeraro Peter R. Cook Davide Marenduzzo A unified-field theory of genome organization and gene regulation iScience Natural sciences Biological sciences Systems biology Data processing in systems biology |
| title | A unified-field theory of genome organization and gene regulation |
| title_full | A unified-field theory of genome organization and gene regulation |
| title_fullStr | A unified-field theory of genome organization and gene regulation |
| title_full_unstemmed | A unified-field theory of genome organization and gene regulation |
| title_short | A unified-field theory of genome organization and gene regulation |
| title_sort | unified field theory of genome organization and gene regulation |
| topic | Natural sciences Biological sciences Systems biology Data processing in systems biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422402443X |
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