{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T13:34:41Z","timestamp":1771076081571,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Gene regulation is a key factor in gaining a full understanding of molecular biology. <jats:italic>Cis<\/jats:italic>-regulatory modules (CRMs), consisting of multiple transcription factor binding sites, have been confirmed as the main regulators in gene expression. In recent years, a novel regulator known as microRNA (miRNA) has been found to play an important role in gene regulation. Meanwhile, transcription factor and microRNA co-regulation has been widely identified. Thus, the relationships between CRMs and microRNAs have generated interest among biologists.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We constructed new combinatorial regulatory modules based on CRMs and miRNAs. By analyzing their effect on gene expression profiles, we found that genes targeted by both CRMs and miRNAs express in a significantly similar way. Furthermore, we constructed a regulatory network composed of CRMs, miRNAs, and their target genes. Investigating its structure, we found that the feed forward loop is a significant network motif, which plays an important role in gene regulation. In addition, we further analyzed the effect of miRNAs in embryonic cells, and we found that mir-154, as well as some other miRNAs, have significant co-regulation effect with CRMs in embryonic development.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Based on the co-regulation of CRMs and miRNAs, we constructed a novel combinatorial regulatory network which was found to play an important role in gene regulation, particularly during embryonic development.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-150","type":"journal-article","created":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T07:16:14Z","timestamp":1289286974000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Combinatorial regulation of transcription factors and microRNAs"],"prefix":"10.1186","volume":"4","author":[{"given":"Naifang","family":"Su","sequence":"first","affiliation":[]},{"given":"Yufu","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Minping","family":"Qian","sequence":"additional","affiliation":[]},{"given":"Minghua","family":"Deng","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,11,8]]},"reference":[{"issue":"33","key":"561_CR1","doi-asserted-by":"publisher","first-page":"12114","DOI":"10.1073\/pnas.0402858101","volume":"101","author":"Q Zhou","year":"2004","unstructured":"Zhou Q, Wong WH: CisModule: De novo discovery of' cis-regulatory modules by hierarchical mixture modeling. 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