Cooperative activation by GATA-4 and YY1 of the cardiac B-type natriuretic peptide promoter.
YY1, a multifunctional protein essential for embryonic development, is a known repressor or activator of transcription. In cardiac and skeletal myocytes, YY1 has been described essentially as a negative regulator of muscle-specific genes. In this study, we report that YY1 is a transcriptional activator of the B-type natriuretic peptide (BNP) gene, which encodes one of the heart major secretory products. YY1 binds an element within the proximal cardiac BNP promoter, in close proximity to the high affinity binding sites for the zinc finger GATA proteins. We show that YY1 cooperates with GATA-4 to synergistically activate BNP transcription. Structure-function analysis revealed that the DNA binding domain of YY1 is sufficient for cooperative interaction with GATA-4, likely through corecruitment of the CREB-binding protein coactivator. The results suggest that YY1 and GATA factors are components of transcriptionally active complexes present in cardiac and other GATA-containing cells.
Laboratoire de Développement et Différenciation Cardiaques, Institut de Recherches Cliniques de Montréal, Université de Montréal, 110 des Pins Ouest, Montréal QC, H2W 1R7, Canada.
S S
SS
Bhalla
L
L
Robitaille
M
M
Nemer
D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020097:Natriuretic Peptide, Brain; D009841:Oligonucleotides / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050991:GATA4 Transcription Factor; D009841:Oligonucleotides; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor