Characterization of the 5′-flanking region and chromosomal assignment of the human brain natriuretic peptide gene

Y. Ogawa, H. Itoh, O. Nakagawa, G. Shirakami, N. Tamura, T. Yoshimasa, K. Nagata, N. Yoshida, K. Nakao

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle, and synthesis and secretion of BNP are greatly augmented in patients with congestive heart failure and in animal models of ventricular hypertrophy. In order to elucidate the molecular mechanisms underlying the human BNP gene expression in the heart, the human BNP gene was isolated from a size-selected genomic minilibrary. The 1.9-kb human BNP 5′-flanking region (-1813 to +110) contained an array of putative cis-acting regulatory elements. Various lengths of the cloned 5′-flanking sequences were linked upstream to the bacterial chloramphenicol acetyltransferase (CAT) gene, and their promoter activities were assayed. The 1.9-kb promoter region showed a high-level CAT activity in cultured neonatal rat ventricular cardiocytes. When the CT-rich sequences (-1288 to -1095) were deleted, the high-level activity was reduced to approximately 30%. The 399-bp BNP 5′ flanking region (-289 to +110) showed approximately 10% activity of the 1.9-kb region. Furthermore, using human-rodent somatic hybrid cell lines, the BNP gene was assigned to human chromosome 1, on which the atrial natriuretic peptide gene is localized. The present study leads to a better understanding of the molecular mechanisms for the human BNP gene expression in the heart.

Original languageEnglish
Pages (from-to)457-463
Number of pages7
JournalJournal of Molecular Medicine
Volume73
Issue number9
DOIs
Publication statusPublished - 1995 Sep 1
Externally publishedYes

Keywords

  • Atrial natriuretic peptide
  • Brain natriuretic peptide
  • Cardiac hormone
  • Chromosomal assignment

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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    Ogawa, Y., Itoh, H., Nakagawa, O., Shirakami, G., Tamura, N., Yoshimasa, T., Nagata, K., Yoshida, N., & Nakao, K. (1995). Characterization of the 5′-flanking region and chromosomal assignment of the human brain natriuretic peptide gene. Journal of Molecular Medicine, 73(9), 457-463. https://doi.org/10.1007/BF00202264