Document Detail

Angiotensinogen gene expression is dependent on signal transducer and activator of transcription 3-mediated p300/cAMP response element binding protein-binding protein coactivator recruitment and histone acetyltransferase activity.
MedLine Citation:
PMID:  11923478     Owner:  NLM     Status:  MEDLINE    
Angiotensin II, a potent vasoactive peptide produced by proteolysis of the angiotensinogen (AGT) prohormone, plays a critical role in cardiovascular homeostasis. Recently we showed that IL-6 induces human (h)AGT transcription by activating the signal transducers and activators of transcription (STATs). Here we investigated the role of the coactivator p300/cAMP response element binding protein-binding protein (CBP) in STAT3-mediated hAGT gene expression. Overexpression of adenovirus 12S E1A, which binds and inactivates p300/CBP, strongly inhibited basal and stimulated hAGT transcription, whereas a mutant E1A defective in binding p300/CBP did not. Conversely, ectopic expression of p300 and CBP potentiated inducible hAGT promoter activity. Coimmunoprecipitation assays revealed STAT3-p300 interaction upon IL-6 stimulation. The STAT3-p300 association requires the STAT3 C-terminal transactivation domain, as STAT3 deleted of transactivation functions as a dominant-negative inhibitor and does not associate with p300/CBP. The observation that IL-6 stimulation increases histone H4 acetylation of the endogenous hAGT promoter, and expression of p300 deficient in histone acetyltransferase activity down-regulates hAGT promoter activity both suggest that p300 histone acetyltransferase activity is required for hAGT expression. Finally, treatment of HepG2 cells with a histone deacetylase inhibitor increased the hAGT mRNA abundance by 2- to 3-fold. Taken together, our results indicate that IL-6-inducible expression of the hAGT promoter is mediated by physical association of the COOH terminus of STAT3 with p300/CBP, the recruitment of which targets histone acetylation and results in chromatin remodeling.
Sutapa Ray; Christopher T Sherman; Muping Lu; Allan R Brasier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  16     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-03-29     Completed Date:  2002-08-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  824-36     Citation Subset:  IM    
Department of Internal Medicine and Sealy Center for Molecular Sciences, The University of Texas Medical Branch, Galveston, Texas 77555-1060, USA.
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MeSH Terms
Acetyltransferases / metabolism*
Adenovirus E1A Proteins / metabolism
Angiotensinogen / genetics*
CREB-Binding Protein
Cell Line
DNA-Binding Proteins / metabolism*
Gene Expression Regulation
Histone Acetyltransferases
Histone Deacetylase Inhibitors
Histones / metabolism
Interleukin-6 / pharmacology
Nuclear Proteins / metabolism*
Promoter Regions, Genetic
RNA, Messenger / metabolism
STAT3 Transcription Factor
Saccharomyces cerevisiae Proteins*
Trans-Activators / metabolism*
Grant Support
Reg. No./Substance:
0/Adenovirus E1A Proteins; 0/CREBBP protein, human; 0/DNA-Binding Proteins; 0/Histone Deacetylase Inhibitors; 0/Histones; 0/Interleukin-6; 0/Nuclear Proteins; 0/RNA, Messenger; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Saccharomyces cerevisiae Proteins; 0/Trans-Activators; 11002-13-4/Angiotensinogen; EC 2.3.1.-/Acetyltransferases; EC Protein; EC Acetyltransferases

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