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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U2 - 10.1007/BF00202264
DO - 10.1007/BF00202264
M3 - Article
C2 - 8528749
AN - SCOPUS:0028885640
VL - 73
SP - 457
EP - 463
JO - Klinische Wochenschrift
JF - Klinische Wochenschrift
SN - 0946-2716
IS - 9
ER -