{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:52:43Z","timestamp":1773665563339,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation:The interaction between transcription factor (TF) and transcription factor binding site (TFBS) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken their interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be compensated by a corresponding mutation in its binding partner during the course of evolution. Confirming this co-evolutionary relationship will guide us in designing protein sequences to target a specific DNA sequence or in predicting TFBS for poorly studied proteins, or even correcting and rescuing disease mutations in clinical applications.<\/jats:p>\n               <jats:p>Results: Based on six, publicly available, experimentally validated TF\u2013TFBS binding datasets for the basic Helix\u2013Loop\u2013Helix (bHLH) family, Homeo family, High-Mobility Group (HMG) family and Transient Receptor Potential channels (TRP) family, we showed that the evolutions of the TFs and their TFBSs are significantly correlated across eukaryotes. We further developed a mutual information-based method to identify co-evolved protein residues and DNA bases. This research sheds light on the dynamic relationship between TF and TFBS during their evolution. The same principle and strategy can be applied to co-evolutionary studies on protein\u2013DNA interactions in other protein families.<\/jats:p>\n               <jats:p>Availability: All the datasets, scripts and other related files have been made freely available at: http:\/\/jjwanglab.org\/co-evo.<\/jats:p>\n               <jats:p>Contact: \u00a0junwen@uw.edu<\/jats:p>\n               <jats:p>Supplementary Information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr503","type":"journal-article","created":{"date-parts":[[2011,9,7]],"date-time":"2011-09-07T00:24:53Z","timestamp":1315355093000},"page":"2972-2978","source":"Crossref","is-referenced-by-count":28,"title":["Correlated evolution of transcription factors and their binding sites"],"prefix":"10.1093","volume":"27","author":[{"given":"Shu","family":"Yang","sequence":"first","affiliation":[{"name":"1 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 2Department of Psychiatry and State Key Laboratory of Cognitive and Brain Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 3Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Dallas, TX, 75080, USA and 4Bioinformatics Division, TNLIST, Tsinghua University, Beijing, 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hari Krishna","family":"Yalamanchili","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 2Department of Psychiatry and State Key Laboratory of Cognitive and Brain Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 3Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Dallas, TX, 75080, USA and 4Bioinformatics Division, TNLIST, Tsinghua University, Beijing, 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Li","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 2Department of Psychiatry and State Key Laboratory of Cognitive and Brain Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 3Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Dallas, TX, 75080, USA and 4Bioinformatics Division, TNLIST, Tsinghua University, Beijing, 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwok-Ming","family":"Yao","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 2Department of Psychiatry and State Key Laboratory of Cognitive and Brain Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 3Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Dallas, TX, 75080, USA and 4Bioinformatics Division, TNLIST, Tsinghua University, Beijing, 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pak Chung","family":"Sham","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 2Department of Psychiatry and State Key Laboratory of Cognitive and Brain Sciences, LKS Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong SAR, China, 3Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Dallas, TX, 75080, USA and 4Bioinformatics Division, 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