article published yes Anna A Nagy-Staron author 3ABC5BA6-F248-11E8-B48F-1D18A9856A870000-0002-1391-8377 Kathrin Tomasek author 3AEC8556-F248-11E8-B48F-1D18A9856A870000-0003-3768-877X Caroline Caruso Carter author Elisabeth Sonnleitner author Bor Kavcic author 350F91D2-F248-11E8-B48F-1D18A9856A870000-0001-6041-254X Tiago Paixão author Calin C Guet author 47F8433E-F248-11E8-B48F-1D18A9856A870000-0001-6220-2052 GaTk department CaGu department The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies project Cybergenetic circuits to test composability of gene networks project Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs. https://research-explorer.ista.ac.at/download/9283/9284/elife-65993-v2.pdf application/pdfno eLife Sciences Publications2021 eng Genetics and Molecular Biology 2050-084X 33683203 00063105090000110.7554/elife.65993 10 https://research-explorer.ista.ac.at/record/8951 Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. <i>eLife</i>. 2021;10. doi:<a href="https://doi.org/10.7554/elife.65993">10.7554/elife.65993</a> Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., &#38; Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/elife.65993">https://doi.org/10.7554/elife.65993</a> A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021). Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993. A. A. Nagy-Staron <i>et al.</i>, “Local genetic context shapes the function of a gene regulatory network,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021. Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>, vol. 10, e65993, eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/elife.65993">10.7554/elife.65993</a>. Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href="https://doi.org/10.7554/elife.65993">https://doi.org/10.7554/elife.65993</a>. 92832021-03-23T10:11:46Z2025-06-12T06:36:17Z