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Thus, it is of utmost importance to understand the transcriptional regulation of TCSs to infer bacterial environmental adaptation and disease pathogenicity. Utilizing a combinatorial approach integrating RNA sequencing (RNA-seq), independent component analysis, chromatin immunoprecipitation coupled with exonuclease treatment (ChIP-exo), and data mining, we suggest five different modes of TCS transcriptional regulation. Our data further highlight noncognate inducers of TCSs, which emphasizes the cross-regulatory nature of TCSs in\n                    <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n                    and suggests that TCSs may have a role beyond their cognate functionalities. In summary, these results can lead to an understanding of the metabolic capabilities of bacteria and correctly predict complex phenotype under diverse conditions, especially when further incorporated with genome-scale metabolic models.\n                  <\/jats:p>","DOI":"10.1128\/msystems.00980-20","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T09:28:17Z","timestamp":1604914097000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships"],"prefix":"10.1128","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9527-7958","authenticated-orcid":false,"given":"Kumari Sonal","family":"Choudhary","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of California, San Diego, San Diego, California, 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