Intronic elements in the Na+/I-symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription
di Dato, V.
di Lauro, R.
Tazebay, U. H.
Nucleic Acids Research
Oxford University Press
3172 - 3185
Item Usage Stats
Activity of the sodium/iodide symporter (NIS) in lactating breast is essential for iodide (I-) accumulation in milk. Significant NIS upregulation was also reported in breast cancer, indicating a potential use of radioiodide treatment. All-trans-retinoic acid (tRA) is a potent ligand that enhances NIS expression in a subset of breast cancer cell lines and in experimental breast cancer models. Indirect tRA stimulation of NIS in breast cancer cells is very well documented; however, direct upregulation by tRA-activated nuclear receptors has not been identified yet. Aiming to uncover cis-acting elements directly regulating NIS expression, we screened evolutionary-conserved non-coding genomic sequences for responsiveness to tRA in MCF-7. Here, we report that a potent enhancer in the first intron of NIS mediates direct regulation by tRA-stimulated nuclear receptors. In vitro as well as in vivo DNA-protein interaction assays revealed direct association between retinoic acid receptor-α (RARα) and retinoid-X-receptor (RXR) with this enhancer. Moreover, using chromatin immunoprecipitation (ChIP) we uncovered early events of NIS transcription in response to tRA, which require the interaction of several novel intronic tRA responsive elements. These findings indicate a complex interplay between nuclear receptors, RNA Pol-II and multiple intronic RAREs in NIS gene, and they establish a novel mechanistic model for tRA-induced gene transcription. © The Author(s) 2010. Published by Oxford University Press.
KeywordsCell nucleus receptor
Retinoic acid receptor
Retinoic acid receptor alpha
Retinoid X receptor
RNA polymerase II
Sodium iodide symporter
Published Version (Please cite this version)http://dx.doi.org/10.1093/nar/gkq023
Showing items related by title, author, creator and subject.
Tincer G.; Bayyurt, B.; Arıca, Y.M.; Gürsel İ. (Turkish Society of Immunology, 2015)Objectives: Chitosan is a widely used vaccine or anti-cancer delivery vehicle. In this study, we investigated the immunomodulatory effect of chitosan/pIC nanocomplexes on mouse immune cells. Materials and methods: Proliferative ...
Quantification of SLIT-ROBO transcripts in hepatocellular carcinoma reveals two groups of genes with coordinate expression Avci, M. E.; Konu, O.; Yagci, T. (BioMed Central, 2008)Background: SLIT-ROBO families of proteins mediate axon pathfinding and their expression is not solely confined to nervous system. Aberrant expression of SLIT-ROBO genes was repeatedly shown in a wide variety of cancers, ...
Cekic, C.; Linden, J. (Nature Publishing Group, 2016)Cellular stress or apoptosis triggers the release of ATP, ADP and other nucleotides into the extracellular space. Extracellular nucleotides function as autocrine and paracrine signalling molecules by activating cell-surface ...