{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:53:06Z","timestamp":1791337986470,"version":"4.3.1"},"reference-count":48,"publisher":"Cold Spring Harbor Laboratory","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1992,11]]},"abstract":"<jats:p>The distal portion of the rat insulin I gene 5'-flanking DNA contains two sequence elements, the Far and FLAT elements, that can function in combination, but not separately, as a beta-cell-specific transcriptional enhancer. We have isolated several cDNAs encoding proteins that bind to the FLAT element. Two of these cDNAs, cdx-3 and lmx-1, represent homeo box containing mRNAs with restricted patterns of expression. The protein encoded by lmx-1 also contains two amino-terminal cysteine\/histidine-rich \"LIM\" domains. Both cdx-3 and lmx-1 can activate transcription of a Far\/FLAT-linked gene when expressed in a normally non-insulin-producing fibroblast cell line. Furthermore, in fibroblasts expressing transfected beta-cell lmx-1, the addition of the Far-binding, basic helix-loop-helix protein shPan-1 (the hamster equivalent of human E47) causes a dramatic synergistic activation. ShPan-1 causes no activation in fibroblasts expressing transfected cdx-3 or the related LIM-homeodomain protein isl-1. Deletion of one or both of the LIM domains from the 5' end of the lmx-1 cDNA removes this synergistic interaction with shPan-1 without any loss of basal transcriptional activation. We conclude that beta-cell lmx-1 functions by binding to the FLAT element and interacting through the LIM-containing amino terminus with shPan-1 bound at the Far element. These proteins form the minimal components for a functional minienhancer complex.<\/jats:p>","DOI":"10.1101\/gad.6.11.2165","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T21:15:46Z","timestamp":1181078146000},"page":"2165-2176","source":"Crossref","is-referenced-by-count":310,"title":["Synergistic activation of the insulin gene by a LIM-homeo domain protein and a basic helix-loop-helix protein: building a functional insulin minienhancer complex."],"prefix":"10.1101","volume":"6","author":[{"given":"M S","family":"German","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R B","family":"Chadwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W J","family":"Rutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1992,11,1]]},"reference":[{"key":"2021111320251030000_6.11.2165.1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.14.3893"},{"key":"2021111320251030000_6.11.2165.2","doi-asserted-by":"crossref","first-page":"8285","DOI":"10.1016\/S0021-9258(19)39070-2","article-title":"Positive and negative regulation of the insulin gene by multiple trans-acting factors,","volume":"265","year":"1990","journal-title":"J. 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