{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:35:40Z","timestamp":1791070540156,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2005,10,12]],"date-time":"2005-10-12T00:00:00Z","timestamp":1129075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Research"],"published-print":{"date-parts":[[2005,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The paired box protein Pax3 is an essential regulator of muscle and neural crest\u2010derived cell types, including melanocytes. Within this lineage, Pax3 has been shown to regulate the genes encoding microphthalmia\u2010associated transcription factor (Mitf) and tyrosinase\u2010related protein\u20101 (Trp\u20101), despite each having dissimilar Pax3 recognition sequences. We have, therefore, examined the structural requirements for Pax3 binding to the <jats:italic>MITF<\/jats:italic> and <jats:italic>TRP\u20101<\/jats:italic> promoter elements, focusing on the contribution of the paired domain and homeodomain to Pax3 target site recognition. Unexpectedly, although the <jats:italic>MITF<\/jats:italic> element is characterized by suboptimal recognition motifs for the paired domain and homeodomain, it sustains a higher level of Pax3 binding than <jats:italic>TRP\u20101<\/jats:italic>, which contains a canonical paired domain site. The basis for this difference involves a context\u2010dependent cooperative binding event requiring both the paired domain and homeodomain, while the paired domain alone is sufficient for <jats:italic>TRP\u20101<\/jats:italic> recognition. Significantly, the analysis of Waardenburg syndrome mutations reveals marked disparity in their effects on <jats:italic>MITF<\/jats:italic> and <jats:italic>TRP\u20101<\/jats:italic> binding that further underscores mechanistic differences in their interaction with Pax3. Importantly, these mutations also exert distinct effects on the ability of Pax3 to regulate reporter genes fused to either the <jats:italic>MITF<\/jats:italic> or <jats:italic>TRP\u20101<\/jats:italic> promoters. Our results, therefore, establish that Pax3 can regulate target genes through alternate modes of DNA recognition that are differentially impacted by disease\u2010causing mutations, which together have important implications for understanding Pax3\u2010regulated gene networks.<\/jats:p>","DOI":"10.1111\/j.1600-0749.2005.00275.x","type":"journal-article","created":{"date-parts":[[2005,10,12]],"date-time":"2005-10-12T15:23:47Z","timestamp":1129130627000},"page":"427-438","source":"Crossref","is-referenced-by-count":27,"title":["Pax3 target gene recognition occurs through distinct modes that are differentially affected by disease\u2010associated mutations"],"prefix":"10.1111","volume":"18","author":[{"given":"Gareth N.","family":"Corry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Alan","family":"Underhill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,10,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402949200"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(98)80008-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)7:1<30::AID-HUMU4>3.0.CO;2-T"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/355637a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki562"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1212"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00345-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.15.3131"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(01)02594-X"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.10.2048"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.20.7673-7684.2000"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90071-6"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)37201-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.20.11719"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.4213"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1781"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1242\/dev.122.9.2697","article-title":"Drosophila Paired regulates late even\u2010skipped expression through a composite binding site for the paired domain and the homeodomain","volume":"122","author":"Fujioka M.","year":"1996","journal-title":"Development"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.38.26894"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb08054.x"},{"key":"e_1_2_6_21_1","first-page":"455","article-title":"Mutations in the paired domain of the human PAX3 gene cause Klein\u2010Waardenburg syndrome (WS\u2010III) as well as Waardenburg syndrome type I (WS\u2010I)","volume":"52","author":"Hoth C.F.","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(90)90132-6"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.9.2639"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.14.2131"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1242\/dev.129.2.527","article-title":"Msx2 is an immediate downstream effector of Pax3 in the development of the murine cardiac neural crest","volume":"129","author":"Kwang S.J.","year":"2002","journal-title":"Development"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10828"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03292"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.8.656"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00336-7"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/355635a0"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0193-26"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00189-6"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.4.594"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1139\/o00-077"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14175"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3692"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0398-283"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.11.2120"}],"container-title":["Pigment Cell Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1600-0749.2005.00275.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1600-0749.2005.00275.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T22:20:21Z","timestamp":1696976421000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1600-0749.2005.00275.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,10,12]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2005,12]]}},"alternative-id":["10.1111\/j.1600-0749.2005.00275.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1600-0749.2005.00275.x","archive":["Portico"],"relation":{},"ISSN":["0893-5785","1600-0749"],"issn-type":[{"value":"0893-5785","type":"print"},{"value":"1600-0749","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,10,12]]}}}