{"publisher":"Nature Publishing Group","scopus_import":1,"oa_version":"Published Version","oa":1,"date_created":"2018-12-11T11:51:34Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"Intrinsic limits to gene regulation by global crosstalk","quality_controlled":"1","status":"public","related_material":{"record":[{"relation":"dissertation_contains","id":"6071","status":"public"}]},"month":"08","date_updated":"2023-09-07T12:53:49Z","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"license":"https://creativecommons.org/licenses/by/4.0/","type":"journal_article","file":[{"date_updated":"2020-07-14T12:44:46Z","date_created":"2018-12-12T10:12:01Z","file_size":861805,"file_id":"4919","relation":"main_file","checksum":"fe3f3a1526d180b29fe691ab11435b78","file_name":"IST-2016-627-v1+1_ncomms12307.pdf","creator":"system","access_level":"open_access","content_type":"application/pdf"},{"checksum":"164864a1a675f3ad80e9917c27aba07f","relation":"main_file","access_level":"open_access","creator":"system","file_name":"IST-2016-627-v1+2_ncomms12307-s1.pdf","content_type":"application/pdf","date_updated":"2020-07-14T12:44:46Z","file_size":1084703,"date_created":"2018-12-12T10:12:02Z","file_id":"4920"}],"day":"04","department":[{"_id":"GaTk"},{"_id":"NiBa"},{"_id":"CaGu"}],"abstract":[{"text":"Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. 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. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements.","lang":"eng"}],"date_published":"2016-08-04T00:00:00Z","publication_status":"published","year":"2016","intvolume":"         7","publist_id":"5887","volume":7,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7"},{"_id":"25B07788-B435-11E9-9278-68D0E5697425","name":"Limits to selection in biology and in evolutionary computation","grant_number":"250152","call_identifier":"FP7"},{"grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"ddc":["576"],"file_date_updated":"2020-07-14T12:44:46Z","author":[{"last_name":"Friedlander","first_name":"Tamar","id":"36A5845C-F248-11E8-B48F-1D18A9856A87","full_name":"Friedlander, Tamar"},{"last_name":"Prizak","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","full_name":"Prizak, Roshan"},{"last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"},{"orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H"},{"first_name":"Gasper","last_name":"Tkacik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455"}],"publication":"Nature Communications","has_accepted_license":"1","doi":"10.1038/ncomms12307","_id":"1358","article_number":"12307","pubrep_id":"627","language":[{"iso":"eng"}],"citation":{"mla":"Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” <i>Nature Communications</i>, vol. 7, 12307, Nature Publishing Group, 2016, doi:<a href=\"https://doi.org/10.1038/ncomms12307\">10.1038/ncomms12307</a>.","ieee":"T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic limits to gene regulation by global crosstalk,” <i>Nature Communications</i>, vol. 7. Nature Publishing Group, 2016.","apa":"Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., &#38; Tkačik, G. (2016). Intrinsic limits to gene regulation by global crosstalk. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncomms12307\">https://doi.org/10.1038/ncomms12307</a>","chicago":"Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” <i>Nature Communications</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ncomms12307\">https://doi.org/10.1038/ncomms12307</a>.","ista":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 7, 12307.","ama":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to gene regulation by global crosstalk. <i>Nature Communications</i>. 2016;7. doi:<a href=\"https://doi.org/10.1038/ncomms12307\">10.1038/ncomms12307</a>","short":"T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (2016)."},"ec_funded":1}