Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene.
The vitamin K-dependent matrix Gla protein ( MGP) is synthesized in a wide variety of tissues such as lung, heart, kidney, cartilage, and bone. Expression of the MGP gene is regulated by various growth factors, steroid hormones, and the vitamin A metabolite retinoic acid (RA). In this report, we present evidence that RA down-regulates MGP gene expression in different rat and human cell lines via endogenous retinoid receptors [ RA receptor ( RAR) and retinoid X receptor (RXR)]. Repression of the human MGP (hMGP) gene is specifically mediated by ligand- activated RAR and RXR. Deletion analysis led to the identification of a novel negative response element (NRE) within the hMGP promoter. DNA binding studies performed with bacterially expressed RAR/RXR reveal the formation of a specific heterodimer/NRE complex. Furthermore, electrophoretic mobility-shift assays performed with proteins from RA-treated cells show that endogenous RAR/RXR binds to the NRE. We demonstrate that the NRE contains a CCAAT box and that both RAR/RXR and CCAAT- binding proteins such as c/ EBP beta recognize this common regulatory sequence in the hMGP promoter. Our results indicate that RA-mediated repression of the hMGP gene is due to binding of liganded RAR/RXR to a novel negative RA response element.[1]References
- Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene. Kirfel, J., Kelter, M., Cancela, L.M., Price, P.A., Schüle, R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg