Send to:

Choose Destination
See comment in PubMed Commons below
Hypertension. 2009 Mar;53(3):549-55. doi: 10.1161/HYPERTENSIONAHA.108.125088. Epub 2009 Jan 12.

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

Author information

  • 1Department of Medicine and Diabetes Center, University of California at San Francisco, USA.


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 - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk