Retinoic acid is a negative regulator of matrix Gla protein gene expression in teleost fish Sparus aurata.
Matrix Gla protein (MGP) is an extracellular mineral-binding protein expressed in several tissues while accumulated only in bone and cartilage under physiological conditions. Although the precise molecular mechanism of action of MGP remains unknown, all available evidence indicates that it acts as a physiological inhibitor of mineralization. This work presents the cloning of gilthead seabream MGP gene (SaMGP) and the functional analysis of its promoter. SaMGP gene was found to be organized in five exons and to be under control of a distal and a proximal promoter, both, capable of activating SaMGP transcription in transient transfections. Furthermore, we present strong evidence that retinoic acid down-regulates SaMGP gene transcription by interacting, through binding of its receptor, with a specific region within distal promoter. Interestingly, the presence of repetitive motifs in the proximity of SaMGP gene regulatory regions suggests that they may modulate promoter accessibility to transcription machinery, as already seen for other genes. This work provides additional evidence of the usefulness of non-mammalian model systems to elucidate the complex regulation of MGP gene transcription.
Conceição
Natércia
N
Centre of Marine Sciences (CCMAR), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
Laizé
Vincent
V
Simões
Brigite
B
Pombinho
António R
AR
Cancela
M Leonor
ML
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D021541:Sea Bream / Q000235:genetics*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014982:Xenopus laevis; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D004247:DNA; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D005346:Fibroblast Growth Factors; D014212:Tretinoin; D000097568:Matrix Gla Protein