{"file":[{"file_size":861805,"relation":"main_file","date_updated":"2020-07-14T12:44:46Z","content_type":"application/pdf","file_id":"4919","file_name":"IST-2016-627-v1+1_ncomms12307.pdf","creator":"system","checksum":"fe3f3a1526d180b29fe691ab11435b78","access_level":"open_access","date_created":"2018-12-12T10:12:01Z"},{"date_created":"2018-12-12T10:12:02Z","checksum":"164864a1a675f3ad80e9917c27aba07f","access_level":"open_access","file_id":"4920","creator":"system","file_name":"IST-2016-627-v1+2_ncomms12307-s1.pdf","date_updated":"2020-07-14T12:44:46Z","content_type":"application/pdf","relation":"main_file","file_size":1084703}],"department":[{"_id":"GaTk"},{"_id":"NiBa"},{"_id":"CaGu"}],"publisher":"Nature Publishing Group","day":"04","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","volume":7,"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"}],"file_date_updated":"2020-07-14T12:44:46Z","date_created":"2018-12-11T11:51:34Z","publication":"Nature Communications","language":[{"iso":"eng"}],"publication_status":"published","scopus_import":1,"_id":"1358","oa":1,"date_published":"2016-08-04T00:00:00Z","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>.","short":"T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications 7 (2016).","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.","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>","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>.","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>","ista":"Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits to gene regulation by global crosstalk. Nature Communications. 7, 12307."},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"intvolume":"         7","project":[{"grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7"},{"name":"Limits to selection in biology and in evolutionary computation","call_identifier":"FP7","grant_number":"250152","_id":"25B07788-B435-11E9-9278-68D0E5697425"},{"name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"}],"title":"Intrinsic limits to gene regulation by global crosstalk","quality_controlled":"1","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"6071"}]},"year":"2016","pubrep_id":"627","month":"08","ec_funded":1,"date_updated":"2023-09-07T12:53:49Z","publist_id":"5887","oa_version":"Published Version","author":[{"last_name":"Friedlander","first_name":"Tamar","id":"36A5845C-F248-11E8-B48F-1D18A9856A87","full_name":"Friedlander, Tamar"},{"full_name":"Prizak, Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","first_name":"Roshan","last_name":"Prizak"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"first_name":"Nicholas H","orcid":"0000-0002-8548-5240","last_name":"Barton","full_name":"Barton, Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper","last_name":"Tkacik","first_name":"Gasper","orcid":"0000-0002-6699-1455"}],"status":"public","article_number":"12307","ddc":["576"],"doi":"10.1038/ncomms12307","type":"journal_article","has_accepted_license":"1"}