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The human uncoupling protein‐3 gene promoter requires myod and is induced by retinoic acid in muscle cells
Author(s) -
Solanes Gemma,
Pedraza Neus,
Iglesias Roser,
Giralt Marta,
Villarroya Francesc
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0363fje
Subject(s) - myod , retinoid x receptor , microbiology and biotechnology , retinoic acid receptor , biology , retinoic acid , myod protein , uncoupling protein , activator (genetics) , gene , skeletal muscle , response element , promoter , myocyte , myogenesis , nuclear receptor , transcription factor , gene expression , biochemistry , endocrinology , adipose tissue , brown adipose tissue
The uncoupling protein‐3 (UCP‐3) gene encodes for a mitochondrial protein expressed preferentially in skeletal muscle. UCP‐3 mRNA is expressed in cultured muscle cells (C2C12 or L6E9) only when differentiated, at which stage UCP‐3 is highly induced by all‐trans retinoic acid (RA). Here we report that human UCP‐3 promoter activity is dependent on MyoD and inducible by all trans ‐RA. The action of all trans ‐RA is increased by co‐transfection with RA receptor (RAR). We have characterized the RA response element that controls the induction by RA in the 5′ noncoding region of the UCP‐3 gene. Deletion and point‐mutation analysis of the hUCP‐3 promoter led us to identify a direct‐repeat element with one base‐pair spacing (DR1) at position −71/−59 responsible for the induction by RA of the activity of the promoter. This DR1 element bound a nuclear protein complex from muscle cells that contain RAR and retinoid X receptor (RXR). In the absence of this element, the promoter became unresponsive to RA, but it was still dependent on MyoD. In conclusion, it has been established that UCP‐3 gene promoter activity is dependent on MyoD, and the first regulatory pathway for UCP‐3 gene promoter regulation has been recognized by identifying RA as a transcriptional activator of the gene.