Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-7-12
pubmed:abstractText
Angiotensinogen (AGT) is the precursor of one of the most important vasoactive hormone angiotensin II and this gene locus is associated with human essential hypertension. AGT is an acute phase protein and its gene expression is regulated by IL-6. Previous studies have identified three potential STAT-3 binding sites (APREs) located between -160 and -280 of the hAGT gene promoter but only APRE-1 (located between -271 and -279) was shown to be a bonafide enhancer for IL-6-induced promoter activity. We show here that APRE-2, located between -236 and -247, is indeed an HNF-1alpha-binding site and plays an important role in basal and IL-6 induced promoter activity of this gene. Our chromatin immunoprecipitation (ChIP) assay shows that HNF-1alpha binds to this region of the hAGT gene promoter and its recruitment is increased in the presence of IL-6 in Hep3B cells. We also show that the promoter activity of a deletion construct containing only 223 bp of the hAGT gene promoter (that contains only APRE-3) is increased after IL-6 treatment. Our ChIP assay shows that IL-6 treatment recruits STAT-3 to APRE-3 and suggests that this is also an IL6 responsive element. We have previously shown that GR binds to the proximal promoter of the hAGT gene. Since GR physically interacts with STAT-3, we propose that transcription factors GR, STAT-3, and HNF-1alpha that bind to the nucleotide sequence located between -160 and -280 of the hAGT gene promoter are responsible for IL-6 induced promoter activity of this gene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C401-10
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17475670-Angiotensinogen, pubmed-meshheading:17475670-Base Sequence, pubmed-meshheading:17475670-Carcinoma, Hepatocellular, pubmed-meshheading:17475670-Cell Line, Tumor, pubmed-meshheading:17475670-Chromatin, pubmed-meshheading:17475670-Chromatin Immunoprecipitation, pubmed-meshheading:17475670-Electrophoretic Mobility Shift Assay, pubmed-meshheading:17475670-Hepatocyte Nuclear Factor 1-alpha, pubmed-meshheading:17475670-Humans, pubmed-meshheading:17475670-Interleukin-6, pubmed-meshheading:17475670-Liver Neoplasms, pubmed-meshheading:17475670-Molecular Sequence Data, pubmed-meshheading:17475670-Mutation, pubmed-meshheading:17475670-Promoter Regions, Genetic, pubmed-meshheading:17475670-RNA, Small Interfering, pubmed-meshheading:17475670-RNA Interference, pubmed-meshheading:17475670-Receptors, Glucocorticoid, pubmed-meshheading:17475670-STAT3 Transcription Factor, pubmed-meshheading:17475670-Transcription, Genetic, pubmed-meshheading:17475670-Transfection
pubmed:year
2007
pubmed:articleTitle
HNF-1alpha plays an important role in IL-6-induced expression of the human angiotensinogen gene.
pubmed:affiliation
Pathology Dept., New York Medical College, Valhalla, NY 10595, USA. sudhir_jain@nymc.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural