Ultrasensitive gene regulation by positive feedback loops in nucleosome modification
Abstract Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretic...
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| Format: | Article |
| Language: | English |
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Springer Nature
2008-04-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2008.21 |
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| _version_ | 1849225759535661056 |
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| author | Kim Sneppen Mille A Micheelsen Ian B Dodd |
| author_facet | Kim Sneppen Mille A Micheelsen Ian B Dodd |
| author_sort | Kim Sneppen |
| collection | DOAJ |
| description | Abstract Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretically that by recruiting a histone‐modifying enzyme, a TF binding non‐cooperatively to a single site can change the balance between opposing positive feedback loops in histone modification to produce a large change in gene expression in response to a small change in concentration of the TF. This mechanism can also generate bistable promoter responses, allowing a gene to be on in some cells and off in others, despite the cells being in identical conditions. In addition, the system provides a simple means by which the activities of many TFs could be integrated at a promoter. |
| format | Article |
| id | doaj-art-4b40e6e6027f4f0c845250d122a2b58f |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2008-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-4b40e6e6027f4f0c845250d122a2b58f2025-08-24T12:01:30ZengSpringer NatureMolecular Systems Biology1744-42922008-04-01411510.1038/msb.2008.21Ultrasensitive gene regulation by positive feedback loops in nucleosome modificationKim Sneppen0Mille A Micheelsen1Ian B Dodd2Center for Models of Life, Niels Bohr InstituteCenter for Models of Life, Niels Bohr InstituteDepartment of Molecular and Biomedical Sciences (Biochemistry), University of AdelaideAbstract Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretically that by recruiting a histone‐modifying enzyme, a TF binding non‐cooperatively to a single site can change the balance between opposing positive feedback loops in histone modification to produce a large change in gene expression in response to a small change in concentration of the TF. This mechanism can also generate bistable promoter responses, allowing a gene to be on in some cells and off in others, despite the cells being in identical conditions. In addition, the system provides a simple means by which the activities of many TFs could be integrated at a promoter.https://doi.org/10.1038/msb.2008.21epigeneticshistone modificationsignal integrationthresholdtranscription factor |
| spellingShingle | Kim Sneppen Mille A Micheelsen Ian B Dodd Ultrasensitive gene regulation by positive feedback loops in nucleosome modification Molecular Systems Biology epigenetics histone modification signal integration threshold transcription factor |
| title | Ultrasensitive gene regulation by positive feedback loops in nucleosome modification |
| title_full | Ultrasensitive gene regulation by positive feedback loops in nucleosome modification |
| title_fullStr | Ultrasensitive gene regulation by positive feedback loops in nucleosome modification |
| title_full_unstemmed | Ultrasensitive gene regulation by positive feedback loops in nucleosome modification |
| title_short | Ultrasensitive gene regulation by positive feedback loops in nucleosome modification |
| title_sort | ultrasensitive gene regulation by positive feedback loops in nucleosome modification |
| topic | epigenetics histone modification signal integration threshold transcription factor |
| url | https://doi.org/10.1038/msb.2008.21 |
| work_keys_str_mv | AT kimsneppen ultrasensitivegeneregulationbypositivefeedbackloopsinnucleosomemodification AT milleamicheelsen ultrasensitivegeneregulationbypositivefeedbackloopsinnucleosomemodification AT ianbdodd ultrasensitivegeneregulationbypositivefeedbackloopsinnucleosomemodification |