{"type":"journal_article","day":"08","month":"12","date_updated":"2023-09-07T12:55:21Z","date_published":"2015-12-08T00:00:00Z","publication_status":"published","issue":"24","department":[{"_id":"GaTk"}],"main_file_link":[{"open_access":"1","url":"http://arxiv.org/abs/1504.05716"}],"abstract":[{"lang":"eng","text":"Gene expression is controlled primarily by interactions between transcription factor proteins (TFs) and the regulatory DNA sequence, a process that can be captured well by thermodynamic models of regulation. These models, however, neglect regulatory crosstalk: the possibility that noncognate TFs could initiate transcription, with potentially disastrous effects for the cell. Here, we estimate the importance of crosstalk, suggest that its avoidance strongly constrains equilibrium models of TF binding, and propose an alternative nonequilibrium scheme that implements kinetic proofreading to suppress erroneous initiation. This proposal is consistent with the observed covalent modifications of the transcriptional apparatus and predicts increased noise in gene expression as a trade-off for improved specificity. Using information theory, we quantify this trade-off to find when optimal proofreading architectures are favored over their equilibrium counterparts. Such architectures exhibit significant super-Poisson noise at low expression in steady state."}],"oa_version":"Preprint","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_created":"2018-12-11T11:52:49Z","publisher":"American Physical Society","scopus_import":1,"title":"Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation","quality_controlled":"1","status":"public","related_material":{"record":[{"status":"public","id":"6473","relation":"part_of_dissertation"}]},"publication":"Physical Review Letters","author":[{"last_name":"Cepeda Humerez","first_name":"Sarah A","id":"3DEE19A4-F248-11E8-B48F-1D18A9856A87","full_name":"Cepeda Humerez, Sarah A"},{"full_name":"Rieckh, Georg","id":"34DA8BD6-F248-11E8-B48F-1D18A9856A87","last_name":"Rieckh","first_name":"Georg"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper","first_name":"Gasper","last_name":"Tkacik"}],"doi":"10.1103/PhysRevLett.115.248101","citation":{"apa":"Cepeda Humerez, S. A., Rieckh, G., &#38; Tkačik, G. (2015). Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation. <i>Physical Review Letters</i>. American Physical Society. <a href=\"https://doi.org/10.1103/PhysRevLett.115.248101\">https://doi.org/10.1103/PhysRevLett.115.248101</a>","ista":"Cepeda Humerez SA, Rieckh G, Tkačik G. 2015. Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation. Physical Review Letters. 115(24), 248101.","chicago":"Cepeda Humerez, Sarah A, Georg Rieckh, and Gašper Tkačik. “Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation.” <i>Physical Review Letters</i>. American Physical Society, 2015. <a href=\"https://doi.org/10.1103/PhysRevLett.115.248101\">https://doi.org/10.1103/PhysRevLett.115.248101</a>.","ama":"Cepeda Humerez SA, Rieckh G, Tkačik G. Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation. <i>Physical Review Letters</i>. 2015;115(24). doi:<a href=\"https://doi.org/10.1103/PhysRevLett.115.248101\">10.1103/PhysRevLett.115.248101</a>","short":"S.A. Cepeda Humerez, G. Rieckh, G. Tkačik, Physical Review Letters 115 (2015).","mla":"Cepeda Humerez, Sarah A., et al. “Stochastic Proofreading Mechanism Alleviates Crosstalk in Transcriptional Regulation.” <i>Physical Review Letters</i>, vol. 115, no. 24, 248101, American Physical Society, 2015, doi:<a href=\"https://doi.org/10.1103/PhysRevLett.115.248101\">10.1103/PhysRevLett.115.248101</a>.","ieee":"S. A. Cepeda Humerez, G. Rieckh, and G. Tkačik, “Stochastic proofreading mechanism alleviates crosstalk in transcriptional regulation,” <i>Physical Review Letters</i>, vol. 115, no. 24. American Physical Society, 2015."},"ec_funded":1,"article_number":"248101","_id":"1576","language":[{"iso":"eng"}],"intvolume":"       115","volume":115,"publist_id":"5595","year":"2015","project":[{"name":"Limits to selection in biology and in evolutionary computation","_id":"25B07788-B435-11E9-9278-68D0E5697425","grant_number":"250152","call_identifier":"FP7"}]}