{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:39:54Z","timestamp":1781109594504,"version":"3.54.1"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,4,29]]},"abstract":"<jats:p>\n                    The steroid hormone 20-hydroxyecdysone (referred to here as ecdysone) directs\n                    <jats:italic>Drosophila<\/jats:italic>\n                    metamorphosis by activating a series of genetic regulatory hierarchies. ETS domain transcription factors encoded by the ecdysone-inducible\n                    <jats:italic>E74<\/jats:italic>\n                    early gene, E74A and E74B, act at the top of these hierarchies to coordinate the induction of target genes. We have ectopically expressed these E74 isoforms to understand their regulatory functions during the onset of metamorphosis. We show that\n                    <jats:italic>E74<\/jats:italic>\n                    can regulate its own transcription, most likely through binding sites within its gene. Ectopic expression of\n                    <jats:italic>E74B<\/jats:italic>\n                    can partially repress the\n                    <jats:italic>E78B<\/jats:italic>\n                    and\n                    <jats:italic>DHR3<\/jats:italic>\n                    orphan receptor genes, suggesting a role for\n                    <jats:italic>E74<\/jats:italic>\n                    in the appropriate timing of early-late gene expression. Furthermore,\n                    <jats:italic>E74A<\/jats:italic>\n                    is both necessary and sufficient for\n                    <jats:italic>E78B<\/jats:italic>\n                    induction, implicating\n                    <jats:italic>E74A<\/jats:italic>\n                    as a key regulator of\n                    <jats:italic>E78B<\/jats:italic>\n                    expression. We also show, consistent with our studies of\n                    <jats:italic>E74<\/jats:italic>\n                    loss-of-function mutations, that E74B is a potent repressor of late gene transcription and E74A is sufficient to prematurely induce the\n                    <jats:italic>L71\u20131<\/jats:italic>\n                    late gene. However, ectopic expression of both Broad-Complex and E74A activators in an\n                    <jats:italic>E74B<\/jats:italic>\n                    mutant background is not sufficient to prematurely induce all late genes, indicating that other factors contribute to this regulatory circuit. These observations demonstrate that the steroid-triggered switch in E74 transcription factor isoforms plays a central role in the proper timing of secondary-response gene expression.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.9.4582","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"4582-4586","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":42,"title":["A steroid-triggered switch in E74 transcription factor isoforms regulates the timing of secondary-response gene\u2009expression"],"prefix":"10.1073","volume":"94","author":[{"given":"Jennifer C.","family":"Fletcher","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Howard Hughes Medical Institute, 5200 Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Paolo","family":"D\u2019Avino","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Howard Hughes Medical Institute, 5200 Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl S.","family":"Thummel","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Howard Hughes Medical Institute, 5200 Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,4,29]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90201-5"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.63.070194.002315"},{"key":"e_1_3_2_3_2","first-page":"899","volume-title":"Hormones and Drosophila Development","author":"Riddiford L M","year":"1993","unstructured":"L M Riddiford Hormones and Drosophila Development, eds M Bate, A Martinez-Arias (Cold Spring Harbor Lab. 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