Transcriptional regulation of guanylyl cyclase/natriuretic peptide receptor-A gene.
Activation of natriuretic peptide receptor-A (NPRA) produces the second messenger cGMP, which plays a pivotal role in maintaining blood pressure and cardiovascular homeostasis. In the present study, we have examined the role of trans-acting factor Ets-1 in transcriptional regulation of Npr1 gene (coding for NPRA). Using deletional analysis of the Npr1 promoter, we have defined a 400 base pair (bp) region as the core promoter, which contains consensus binding sites for transcription factors including: Ets-1, Lyf-1, and GATA-1/2. Overexpression of Ets-1 in mouse mesangial cells (MMCs) enhanced Npr1 gene transcription by 12-fold. However, overexpression of GATA-1 or Lyf-1 repressed Npr1 basal promoter activity by 50% and 80%, respectively. The constructs having a mutant Ets-1 binding site or lacking this site failed to respond to Ets-1 activation of Npr1 gene transcription. Collectively, the present results demonstrate that Ets-1 greatly stimulates Npr1 gene promoter activity, implicating its critical role in the regulation and function of NPRA at the molecular level.
Kumar
Prerna
P
Department of Physiology, SL-39, Tulane University Health Sciences Center and School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112, USA.
Arise
Kiran K
KK
Pandey
Kailash N
KN
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001794:Blood Pressure; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000096:biosynthesis* / Q000235:genetics; D050527:Mesangial Cells / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D050784:Proto-Oncogene Protein c-ets-1; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A