| Autor: |
Friedlander, Tamar, Prizak, Roshan, Guet, Călin C., Barton, Nicholas H., Tkačik, Gašper |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Nature Communications 7:12307 (2016) |
| Druh dokumentu: |
Working Paper |
| DOI: |
10.1038/ncomms12307 |
| Popis: |
Gene regulation relies on the specificity of transcription factor (TF) - DNA interactions. In equilibrium, limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF-DNA interactions or remains erroneously inactive. We present a tractable biophysical model of global crosstalk, where many genes are simultaneously regulated by many TFs. We show that in the simplest regulatory scenario, a lower bound on crosstalk severity can be analytically derived solely from the number of (co)regulated genes and a suitable parameter that describes binding site similarity. Estimates show that crosstalk could present a significant challenge for organisms with low-specificity TFs, such as metazoans, unless they use appropriate regulation schemes. Strong cooperativity substantially decreases crosstalk, while joint regulation by activators and repressors, surprisingly, does not; moreover, certain microscopic details about promoter architecture emerge as globally important determinants of crosstalk strength. Our results suggest that crosstalk imposes a new type of global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints acting at the level of individual gene regulatory elements. |
| Databáze: |
arXiv |
| Externí odkaz: |
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