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 language | English |
|---|---|
| Pages (from-to) | 457-463 |
| Number of pages | 7 |
| Journal | Journal of Molecular Medicine |
| Volume | 73 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 1995 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
- Genetics(clinical)
Cite this
Characterization of the 5′-flanking region and chromosomal assignment of the human brain natriuretic peptide gene. / Ogawa, Y.; Itoh, H.; Nakagawa, O.; Shirakami, G.; Tamura, N.; Yoshimasa, T.; Nagata, K.; Yoshida, N.; Nakao, K.
In: Journal of Molecular Medicine, Vol. 73, No. 9, 01.09.1995, p. 457-463.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of the 5′-flanking region and chromosomal assignment of the human brain natriuretic peptide gene
AU - Ogawa, Y.
AU - Itoh, H.
AU - Nakagawa, O.
AU - Shirakami, G.
AU - Tamura, N.
AU - Yoshimasa, T.
AU - Nagata, K.
AU - Yoshida, N.
AU - Nakao, K.
PY - 1995/9/1
Y1 - 1995/9/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0028885640&partnerID=8YFLogxK
U2 - 10.1007/BF00202264
DO - 10.1007/BF00202264
M3 - Article
C2 - 8528749
AN - SCOPUS:0028885640
VL - 73
SP - 457
EP - 463
JO - Clinical Investigator
JF - Clinical Investigator
SN - 0946-2716
IS - 9
ER -