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Endothelin-stimulated human B-type natriuretic peptide gene expression is mediated by Yin Yang 1 in association with histone deacetylase 2.

Increased B-type natriuretic peptide (BNP) gene expression is regarded as one of the hallmarks of cardiac myocyte hypertrophy. Here we demonstrate that both basal- and endothelin-1-dependent stimulation of human (h) BNP gene transcription requires the presence of an intact Yin Yang 1 (YY1) binding site positioned at -62 bp relative to the transcription start site. Mutation of this site reduced both basal and stimulated hBNP promoter activity. This site was shown to bind YY1 both in vitro and within the context of the intact cell. The latter interaction increased after endothelin-1 treatment. Exposure to endothelin-1 also resulted in increased nuclear localization of YY1 and a reduction in acetylation of the YY1 protein. Overexpression of wild-type YY1 increased both basal and endothelin-stimulated hBNP promoter activity, whereas a carboxy-terminal deletion mutant of YY1 was devoid of activity. Treatment with the histone deacetylase inhibitor trichostatin A resulted in decreased hBNP reporter activity. YY1 was shown to associate with histone deacetylase 2, and histone deacetylase 2 was shown to associate directly with the hBNP promoter in the intact cell. Collectively these findings demonstrate that YY1 plays an important role in regulating the transcriptional activity of the hBNP gene promoter. These data suggest a model in which YY1 activates hBNP transcription through interaction with histone deacetylase 2.

Pubmed ID: 19139378

Authors

  • Glenn DJ
  • Wang F
  • Chen S
  • Nishimoto M
  • Gardner DG

Journal

Hypertension

Publication Data

March 20, 2009

Associated Grants

  • Agency: NHLBI NIH HHS, Id: F32 HL086158
  • Agency: NHLBI NIH HHS, Id: F32 HL086158
  • Agency: NHLBI NIH HHS, Id: F32 HL086158-02
  • Agency: NHLBI NIH HHS, Id: HL45637
  • Agency: NHLBI NIH HHS, Id: R01 HL045637
  • Agency: NHLBI NIH HHS, Id: R01 HL045637-16

Mesh Terms

  • Animals
  • Cell Nucleus
  • Cells, Cultured
  • Endothelin-1
  • Enzyme Inhibitors
  • Gene Expression Regulation
  • Histone Deacetylase 2
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases
  • Humans
  • Hydroxamic Acids
  • Myocytes, Cardiac
  • Natriuretic Peptide, Brain
  • Promoter Regions, Genetic
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins
  • Transfection
  • YY1 Transcription Factor