{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:52:57Z","timestamp":1791345177156,"version":"4.3.1"},"reference-count":61,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The expression of estrogen-related receptor-\u03b1 (ERR\u03b1) is stimulated by estrogen in selective tissues. Recently, a correlation between ERR\u03b1 expression and the induction of peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 (PGC-1\u03b1) in the liver of fasting animals and in cold-stressed brown-fat tissues and skeletal muscle was shown. To explore the molecular mechanisms of ERR\u03b1 regulation by diverse signals, the promoter of the human ERR\u03b1 gene was cloned and characterized. Mutation and deletion analyses revealed that a 53 bp region containing repeated core element AGGTCA motifs of the ERR\u03b1 gene serves as a multi-hormone response element (MHRE) for several nuclear receptors in transient co-transfection studies of human endometrial carcinoma (HEC-1B) cells. Among the nuclear receptors tested, ERR\u03b3 bound to and robustly stimulated the transcription of reporters containing at least two AGGTCA motifs. Ectopic expression of PGC-1\u03b1 in HEC-1B cells strongly activated the reporter containing the MHRE, presumably via the endogenous nuclear receptor binding to the element. Reducing the endogenous level of ERR\u03b3 by small interfering RNA, and increasing the ERR\u03b3 level by ectopic expression, substantially decreased and increased respectively the transactivation capability of PGC-1\u03b1. The activation function 2 domain of the ERR\u03b3 and the L2 and L3 motifs of PGC-1\u03b1 were essential to transactivate the MHRE. Additionally, PGC-1\u03b1 increases the amount of endogenous ERR\u03b3 bound to the MHRE region as determined by a chromatin immunoprecipitation assay. The present study demonstrates that the MHRE of the ERR\u03b1 gene is a target for ERR\u03b3 transactivation, which is enhanced by PGC-1\u03b1.<\/jats:p>","DOI":"10.1677\/jme.1.01586","type":"journal-article","created":{"date-parts":[[2005,4,8]],"date-time":"2005-04-08T13:13:01Z","timestamp":1112965981000},"page":"473-487","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":50,"title":["Estrogen-related receptor-\u03b3 and peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 regulate estrogen-related receptor-\u03b1 gene expression via a conserved multi-hormone response element"],"prefix":"10.1530","volume":"34","author":[{"given":"D","family":"Liu","sequence":"first","affiliation":[{"name":"Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Zhang","sequence":"additional","affiliation":[{"name":"Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C T","family":"Teng","sequence":"additional","affiliation":[{"name":"Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026070808062162400_BONNELYE-ETAL-1997","doi-asserted-by":"crossref","unstructured":"Bonnelye\n            E\n          , Vanacker JM, Spruyt N, Alric S, Fournier B, Desbiens X & Laudet V 1997 Expression of the estrogen-related receptor 1 (ERR-1) orphan receptor during mouse development. 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