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

Mol Endocrinol. 2002 Apr;16(4):824-36. doi: 10.1210/mend.16.4.0811.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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
  • Humans
  • Interleukin-6 / pharmacology
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • STAT3 Transcription Factor
  • Saccharomyces cerevisiae Proteins*
  • Trans-Activators / metabolism*


  • Adenovirus E1A Proteins
  • DNA-Binding Proteins
  • Histone Deacetylase Inhibitors
  • Histones
  • Interleukin-6
  • Nuclear Proteins
  • RNA, Messenger
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Angiotensinogen
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases