{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T07:38:11Z","timestamp":1772264291751,"version":"3.50.1"},"reference-count":37,"publisher":"Proceedings of the National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,1,22]]},"abstract":"<jats:p>\n                    Metazoan genomes contain vast tracts of cis-regulatory DNA that have been identified typically through tedious functional assays. As a result, it has not been possible to uncover a cis-regulatory code that links primary DNA sequences to gene expression patterns. In an initial effort to determine whether coordinately regulated genes share a common \u201cgrammar,\u201d we have examined the distribution of Dorsal recognition sequences in the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    genome. Dorsal is one of the best-characterized sequence-specific transcription factors in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    . The homeobox gene zerknullt (\n                    <jats:italic>zen<\/jats:italic>\n                    ) is repressed directly by Dorsal, and this repression is mediated by a 600-bp silencer, the ventral repression element (VRE), which contains four optimal Dorsal binding sites. The arrangement and sequence of the Dorsal recognition sequences in the VRE were used to develop a computational algorithm to search the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    genome for clusters of optimal Dorsal binding sites. There are 15 regions in the genome that contain three or more optimal sites within a span of 400 bp or less. Three of these regions are associated with known Dorsal target genes:\n                    <jats:italic>sog<\/jats:italic>\n                    ,\n                    <jats:italic>zen<\/jats:italic>\n                    , and\n                    <jats:italic>Brinker<\/jats:italic>\n                    . The Dorsal binding cluster in\n                    <jats:italic>sog<\/jats:italic>\n                    is shown to mediate lateral stripes of gene expression in response to low levels of the Dorsal gradient. Two of the remaining 12 clusters are shown to be associated with genes that exhibit asymmetric patterns of expression across the dorsoventral axis. These results suggest that bioinformatics can be used to identify novel target genes and associated regulatory DNAs in a gene network.\n                  <\/jats:p>","DOI":"10.1073\/pnas.012591199","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"763-768","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":278,"title":["Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the\n                    <i>Drosophila<\/i>\n                    embryo"],"prefix":"10.1073","volume":"99","author":[{"given":"Michele","family":"Markstein","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720; Committee on Developmental Biology, University of Chicago, Cummings Life Sciences Center 755, 920 East 58th Street, Chicago, IL 60637; Hewlett\u2013Packard Labs, 1501 Page Mill Road, Palo Alto, CA 94304; and in silico Labs, SRX 96, Woodside, CA 94062"}]},{"given":"Peter","family":"Markstein","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720; Committee on Developmental Biology, University of Chicago, Cummings Life Sciences Center 755, 920 East 58th Street, Chicago, IL 60637; Hewlett\u2013Packard Labs, 1501 Page Mill Road, Palo Alto, CA 94304; and in silico Labs, SRX 96, Woodside, CA 94062"}]},{"given":"Vicky","family":"Markstein","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720; Committee on Developmental Biology, University of Chicago, Cummings Life Sciences Center 755, 920 East 58th Street, Chicago, IL 60637; Hewlett\u2013Packard Labs, 1501 Page Mill Road, Palo Alto, CA 94304; and in silico Labs, SRX 96, Woodside, CA 94062"}]},{"given":"Michael S.","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720; Committee on Developmental Biology, University of Chicago, Cummings Life Sciences Center 755, 920 East 58th Street, Chicago, IL 60637; Hewlett\u2013Packard Labs, 1501 Page Mill Road, Palo Alto, CA 94304; and in silico Labs, SRX 96, Woodside, CA 94062"}]}],"member":"341","published-online":{"date-parts":[[2001,12,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35057062"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058040"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3118464"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90651-E"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90772-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90773-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90774-5"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.15.1963"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90014-P"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.10.1892"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.10.1881"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.8.1518"},{"key":"e_1_3_3_13_2","first-page":"171","volume":"7","author":"Kasai 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