Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene. | - CCMAR -

Journal Article

TítuloIdentification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene.
Publication TypeJournal Article
AuthorsKirfel, J, Kelter, M, M. Cancela, L, Price, PA, Schüle, R
Year of Publication1997
JournalProc Natl Acad Sci U S A
Volume94
Questão6
Date Published1997 Mar 18
Pagination2227-32
ISSN0027-8424
Palavras-chaveAnimals, Base Sequence, Binding Sites, Calcium-Binding Proteins, Cell Line, DNA, DNA-Binding Proteins, Extracellular Matrix Proteins, Gene Expression Regulation, Humans, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Rats, Receptors, Retinoic Acid, Recombinant Proteins, Retinoid X Receptors, Sequence Deletion, Transcription Factors, Transfection, Tretinoin, Vitamin K
Abstract

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.

Sapientia

http://www.ncbi.nlm.nih.gov/pubmed/9122176?dopt=Abstract

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID9122176
PubMed Central IDPMC20069
Grant ListAR25921 / AR / NIAMS NIH HHS / United States
CCMAR Authors