{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:21:27Z","timestamp":1779164487072,"version":"3.51.4"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"S1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the post-transcriptional level. Recent studies have suggested that miRNAs and transcription factors are primary metazoan gene regulators; however, the crosstalk between them still remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We proposed a novel model utilizing functional annotation information to identify significant coregulation between transcriptional and post-transcriptional layers. Based on this model, function-enriched coregulation relationships were discovered and combined into different kinds of functional coregulation networks.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We found that miRNAs may engage in a wider diversity of biological processes by coordinating with transcription factors, and this kind of cross-layer coregulation may have higher specificity than intra-layer coregulation. In addition, the coregulation networks reveal several types of network motifs, including feed-forward loops and massive upstream crosstalk. Finally, the expression patterns of these coregulation pairs in normal and tumour tissues were analyzed. Different coregulation types show unique expression correlation trends. More importantly, the disruption of coregulation may be associated with cancers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our findings elucidate the combinatorial and cooperative properties of transcription factors and miRNAs regulation, and we proposes that the coordinated regulation may play an important role in many biological processes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-12-s1-s41","type":"journal-article","created":{"date-parts":[[2011,2,18]],"date-time":"2011-02-18T20:06:30Z","timestamp":1298059590000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Coregulation of transcription factors and microRNAs in human transcriptional regulatory network"],"prefix":"10.1186","volume":"12","author":[{"given":"Cho-Yi","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shui-Tein","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiou-Shann","family":"Fuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsueh-Fen","family":"Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan-Cheng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"4399_CR1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/ng881","volume":"31","author":"SS Shen-Orr","year":"2002","unstructured":"Shen-Orr SS, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 2002, 31: 64\u201368. 10.1038\/ng881","journal-title":"Nat Genet"},{"key":"4399_CR2","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1126\/science.1075090","volume":"298","author":"TI Lee","year":"2002","unstructured":"Lee TI, Rinaldi NJ, Robert F, Odom DT, Bar-Joseph Z, Gerber GK, Hannett NM, Harbison CT, Thompson CM, Simon I, et al.: Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 2002, 298: 799\u2013804. 10.1126\/science.1075090","journal-title":"Science"},{"key":"4399_CR3","doi-asserted-by":"publisher","first-page":"14724","DOI":"10.1073\/pnas.0508637103","volume":"103","author":"H Yu","year":"2006","unstructured":"Yu H, Gerstein M: Genomic analysis of the hierarchical structure of regulatory networks. Proc Natl Acad Sci U S A 2006, 103: 14724\u201314731. 10.1073\/pnas.0508637103","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4399_CR4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","volume":"116","author":"DP Bartel","year":"2004","unstructured":"Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116: 281\u2013297. 10.1016\/S0092-8674(04)00045-5","journal-title":"Cell"},{"key":"4399_CR5","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tig.2006.01.003","volume":"22","author":"VN Kim","year":"2006","unstructured":"Kim VN, Nam JW: Genomics of microRNA. Trends Genet 2006, 22: 165\u2013173. 10.1016\/j.tig.2006.01.003","journal-title":"Trends Genet"},{"key":"4399_CR6","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/nrg2455","volume":"9","author":"AS Flynt","year":"2008","unstructured":"Flynt AS, Lai EC: Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 2008, 9: 831\u2013842. 10.1038\/nrg2455","journal-title":"Nat Rev Genet"},{"key":"4399_CR7","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1126\/science.1151651","volume":"319","author":"O Hobert","year":"2008","unstructured":"Hobert O: Gene Regulation by Transcription Factors and MicroRNAs. Science 2008, 319: 1785\u20131786. 10.1126\/science.1151651","journal-title":"Science"},{"key":"4399_CR8","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.bbrc.2006.11.080","volume":"352","author":"Q Cui","year":"2007","unstructured":"Cui Q, Yu Z, Pan Y, Purisima EO, Wang E: MicroRNAs preferentially target the genes with high transcriptional regulation complexity. Biochem Biophys Res Commun 2007, 352: 733\u2013738. 10.1016\/j.bbrc.2006.11.080","journal-title":"Biochem Biophys Res Commun"},{"key":"4399_CR9","doi-asserted-by":"publisher","first-page":"e131","DOI":"10.1371\/journal.pcbi.0030131","volume":"3","author":"R Shalgi","year":"2007","unstructured":"Shalgi R, Lieber D, Oren M, Pilpel Y: Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comput Biol 2007, 3: e131. 10.1371\/journal.pcbi.0030131","journal-title":"PLoS Comput Biol"},{"key":"4399_CR10","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1186\/1471-2164-8-396","volume":"8","author":"Y Zhou","year":"2007","unstructured":"Zhou Y, Ferguson J, Chang JT, Kluger Y: Inter- and intra-combinatorial regulation by transcription factors and microRNAs. BMC Genomics 2007, 8: 396. 10.1186\/1471-2164-8-396","journal-title":"BMC Genomics"},{"key":"4399_CR11","doi-asserted-by":"publisher","first-page":"D137","DOI":"10.1093\/nar\/gkl1041","volume":"35","author":"C Jiang","year":"2007","unstructured":"Jiang C, Xuan Z, Zhao F, Zhang MQ: TRED: a transcriptional regulatory element database, new entries and other development. Nucleic Acids Res 2007, 35: D137\u2013140. 10.1093\/nar\/gkl1041","journal-title":"Nucleic Acids Res"},{"key":"4399_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","volume":"120","author":"BP Lewis","year":"2005","unstructured":"Lewis BP, Burge CB, Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005, 120: 15\u201320. 10.1016\/j.cell.2004.12.035","journal-title":"Cell"},{"key":"4399_CR13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1261\/rna.7240905","volume":"11","author":"S Baskerville","year":"2005","unstructured":"Baskerville S, Bartel DP: Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 2005, 11: 241\u2013247. 10.1261\/rna.7240905","journal-title":"RNA"},{"key":"4399_CR14","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/nrm1644","volume":"6","author":"VN Kim","year":"2005","unstructured":"Kim VN: MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 2005, 6: 376\u2013385. 10.1038\/nrm1644","journal-title":"Nat Rev Mol Cell Biol"},{"key":"4399_CR15","doi-asserted-by":"publisher","first-page":"D154","DOI":"10.1093\/nar\/gkm952","volume":"36","author":"S Griffiths-Jones","year":"2008","unstructured":"Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ: miRBase: tools for microRNA genomics. Nucl Acids Res 2008, 36: D154\u2013158. 10.1093\/nar\/gkm952","journal-title":"Nucl Acids Res"},{"key":"4399_CR16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","volume":"25","author":"M Ashburner","year":"2000","unstructured":"Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al.: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25: 25\u201329. 10.1038\/75556","journal-title":"Nat Genet"},{"key":"4399_CR17","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0166-4328(01)00297-2","volume":"125","author":"Y Benjamini","year":"2001","unstructured":"Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I: Controlling the false discovery rate in behavior genetics research. Behav Brain Res 2001, 125: 279\u2013284. 10.1016\/S0166-4328(01)00297-2","journal-title":"Behav Brain Res"},{"key":"4399_CR18","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/nature03702","volume":"435","author":"J Lu","year":"2005","unstructured":"Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al.: MicroRNA expression profiles classify human cancers. Nature 2005, 435: 834\u2013838. 10.1038\/nature03702","journal-title":"Nature"},{"key":"4399_CR19","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1126\/science.298.5594.824","volume":"298","author":"R Milo","year":"2002","unstructured":"Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U: Network motifs: simple building blocks of complex networks. Science 2002, 298: 824\u2013827. 10.1126\/science.298.5594.824","journal-title":"Science"},{"key":"4399_CR20","doi-asserted-by":"publisher","first-page":"11980","DOI":"10.1073\/pnas.2133841100","volume":"100","author":"S Mangan","year":"2003","unstructured":"Mangan S, Alon U: Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci U S A 2003, 100: 11980\u201311985. 10.1073\/pnas.2133841100","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4399_CR21","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.molcel.2007.05.018","volume":"26","author":"J Tsang","year":"2007","unstructured":"Tsang J, Zhu J, van Oudenaarden A: MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell 2007, 26: 753\u2013767. 10.1016\/j.molcel.2007.05.018","journal-title":"Mol Cell"},{"key":"4399_CR22","volume-title":"Mol Syst Biol","author":"R Brosh","year":"2008","unstructured":"Brosh R, Shalgi R, Liran A, Landan G, Korotayev K, Nguyen GH, Enerly E, Johnsen H, Buganim Y, Solomon H, et al.: p53-repressed miRNAs are involved with E2F in a feed-forward loop promoting proliferation. Mol Syst Biol 2008., 4: 10.1038\/msb.2008.65"},{"key":"4399_CR23","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.tibs.2004.07.001","volume":"29","author":"O Hobert","year":"2004","unstructured":"Hobert O: Common logic of transcription factor and microRNA action. Trends Biochem Sci 2004, 29: 462\u2013468. 10.1016\/j.tibs.2004.07.001","journal-title":"Trends Biochem Sci"},{"key":"4399_CR24","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.cell.2008.07.020","volume":"134","author":"A Marson","year":"2008","unstructured":"Marson A, Levine SS, Cole MF, Frampton GM, Brambrink T, Johnstone S, Guenther MG, Johnston WK, Wernig M, Newman J, et al.: Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells. Cell 2008, 134: 521\u2013533. 10.1016\/j.cell.2008.07.020","journal-title":"Cell"},{"key":"4399_CR25","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1186\/gb-2003-5-1-r1","volume":"5","author":"A Enright","year":"2003","unstructured":"Enright A, John B, Gaul U, Tuschl T, Sander C, Marks D: MicroRNA targets in Drosophila. Genome Biology 2003, 5: R1. 10.1186\/gb-2003-5-1-r1","journal-title":"Genome Biology"},{"key":"4399_CR26","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/ng1251","volume":"35","author":"E Wienholds","year":"2003","unstructured":"Wienholds E, Koudijs MJ, van Eeden FJ, Cuppen E, Plasterk RH: The microRNA-producing enzyme Dicer1 is essential for zebrafish development. Nat Genet 2003, 35: 217\u2013218. 10.1038\/ng1251","journal-title":"Nat Genet"},{"key":"4399_CR27","first-page":"18","volume":"1","author":"DTS Wu","year":"2008","unstructured":"Wu DTS, Chen JS, Chang DC, Lin S-L: Mir-434\u20135p mediates skin whitening and lightening. Clinical, Cosmetic and Investigational Dermatology 2008, 1: 18.","journal-title":"Clinical, Cosmetic and Investigational Dermatology"},{"key":"4399_CR28","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1158\/0008-5472.CAN-07-2912","volume":"68","author":"LT Bemis","year":"2008","unstructured":"Bemis LT, Chen R, Amato CM, Classen EH, Robinson SE, Coffey DG, Erickson PF, Shellman YG, Robinson WA: MicroRNA-137 targets microphthalmia-associated transcription factor in melanoma cell lines. Cancer Res 2008, 68: 1362\u20131368. 10.1158\/0008-5472.CAN-07-2912","journal-title":"Cancer Res"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-12-S1-S41.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T13:56:31Z","timestamp":1630504591000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-12-S1-S41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,15]]},"references-count":28,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["4399"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-12-s1-s41","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,15]]},"assertion":[{"value":"15 February 2011","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"S41"}}