RGD Reference Report - Identification of two nuclear factor of activated T-cells (NFAT)-response elements in the 5'-upstream regulatory region of the ET-1 promoter. - Rat Genome Database

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Identification of two nuclear factor of activated T-cells (NFAT)-response elements in the 5'-upstream regulatory region of the ET-1 promoter.

Authors: Strait, KA  Stricklett, PK  Kohan, RM  Kohan, DE 
Citation: Strait KA, etal., J Biol Chem. 2010 Sep 10;285(37):28520-8. Epub 2010 Jul 20.
RGD ID: 4144841
Pubmed: PMID:20647310   (View Abstract at PubMed)
PMCID: PMC2937878   (View Article at PubMed Central)
DOI: DOI:10.1074/jbc.M110.153189   (Journal Full-text)

Collecting duct-derived ET-1 regulates salt excretion and blood pressure. We have reported the presence of an inner medullary collecting duct (IMCD)-specific enhancer region in the 5'-upstream ET-1 promoter (Strait, K. A., Stricklett, P. K., Kohan, J. L., Miller, M. B., and Kohan, D. E. (2007) Am. J. Physiol. Renal Physiol. 293, F601-F606). The current studies provide further characterization of the ET-1 5'-upstream distal promoter to identify the IMCD-specific enhancer elements. Deletion studies identified two regions of the 5'-upstream ET-1 promoter, -1725 to -1319 bp and -1319 to -1026 bp, which were required for maximal promoter activity in transfected rat IMCD cells. Transcription factor binding site analysis of these regions identified two consensus nuclear factor of activated T-cells (NFAT) binding sites at -1263 and -1563. EMSA analysis using nuclear extracts from IMCD cells showed that both the -1263 and the -1563 NFAT sites in the ET-1 distal promoter competed for NFAT binding to previously identified NFAT sites in the IL-2 and TNF genes. Gel supershift analysis showed that each of the NFAT binding sites in the ET-1 promoter bound NFAT proteins derived from IMCD nuclear extracts, but they selectively bound different NFAT isoforms; ET-1263 bound NFATc1, whereas ET-1563 bound NFATc3. Site-directed mutagenesis of either the ET-1263 or the ET-1563 sites prevented NFAT binding and reduced ET-1 promoter activity. Thus, NFAT appears to be an important regulator of ET-1 transcription in IMCD cells, and thus, it may play a role in controlling blood pressure through ET-1 regulation of renal salt excretion.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EDN1Humanbronchopulmonary dysplasia  ISOEdn1 (Rattus norvegicus)protein:increased expression:lung (rat)RGD 
Edn1Ratbronchopulmonary dysplasia  IEP protein:increased expression:lung (rat)RGD 
Edn1Mousebronchopulmonary dysplasia  ISOEdn1 (Rattus norvegicus)protein:increased expression:lung (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Edn1  (endothelin 1)

Genes (Mus musculus)
Edn1  (endothelin 1)

Genes (Homo sapiens)
EDN1  (endothelin 1)


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