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We present a direct statistical approach to find overrepresented transcription factor binding sites in a foreground promoter sequence set against a background promoter sequence set. Our approach naturally extends to synergistic transcription factor binding site search.<\/jats:p><jats:p>We find putative transcription factor binding sites that are overrepresented in the proximal promoters of liver-specific genes relative to proximal promoters of liver-independent genes. Our results indicate that binding sites for hepatocyte nuclear factors (especially HNF-1 and HNF-4) and CCAAT\/enhancer-binding protein (C\/EBP\u03b2) are the most overrepresented in proximal promoters of liver-specific genes. Our results suggest that HNF-4 has strong synergistic relationships with HNF-1, HNF-4 and HNF-3\u03b2 and with C\/EBP\u03b2.<\/jats:p><jats:p>Availability: Programs are available for use over the Web at http:\/\/rulai.cshl.edu\/tools\/dwe<\/jats:p><jats:p>Contact: \u00a0ps@cs.pdx.edu; mzhang@cshl.edu<\/jats:p><jats:p>Supplementary information: Data and omitted results are available at http:\/\/rulai.cshl.edu\/tools\/dwe\/supp<\/jats:p>","DOI":"10.1093\/bioinformatics\/bth471","type":"journal-article","created":{"date-parts":[[2004,8,28]],"date-time":"2004-08-28T01:15:02Z","timestamp":1093655702000},"page":"31-38","source":"Crossref","is-referenced-by-count":26,"title":["DWE: Discriminating Word Enumerator"],"prefix":"10.1093","volume":"21","author":[{"given":"Pavel","family":"Sumazin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gengxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Hata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Q.","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,8,27]]},"reference":[{"key":"2023013107191997900_B1","doi-asserted-by":"crossref","unstructured":"Agresti, A. 1992A survey of exact inference for contingency tables. 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