TY - JOUR
T1 - Cloning and characterization of the murine Pkd2 promoter
AU - Park, Jong Hoon
AU - Li, Li
AU - Cai, Yiqiang
AU - Hayashi, Tomohito
AU - Dong, Feng
AU - Maeda, Yoshiko
AU - Rubin, Charles
AU - Somlo, Stefan
AU - Wu, Guanqing
N1 - Funding Information:
We thank Rongguang Yang for sequence analysis. This study was supported by grants from National Institutes of Health (P50 DK573280) to S.S. and by grants from the Polycystic Kidney Disease Research Foundation (97018) and the American Heart Association (9930213N) to G.W.
PY - 2000/6/15
Y1 - 2000/6/15
N2 - Pkd2, the mouse homologue of PKD2, the gene responsible for the second form of autosomal dominant polycystic kidney disease, is highly expressed in fetal and adult mouse tissues. The expression of Pkd2 is developmentally regulated. To begin to dissect out the regulatory mechanism of Pkd2 expression, we characterized the basic features of the gene structure and identified potential cis-regulatory elements of Pkd2 transcription. Pkd2 spans 42 kb with a transcription start site 165 bp upstream of the translation start codon. Exon 1 of Pkd2 is 755 bp long, and the full-length transcript is 5215 bp. The Pkd2 promoter region is GC-rich and lacks a consensus TATA or CCAAT box. Consensus binding sites for the transcription factors Sp-1, NF-1, and Ap-2 lie in the 5' upstream region of Pkd2. The Sp-1 binding site is conserved in 5' upstream sequences of both the mouse and the human genes. The CAT activity of a series of upstream segments from +178 to -2749 was assessed in MDCK, LLCPK1, COS-7, and HEK293 cells. Deletion analysis identified a 409-bp fragment from position -221 to +178 responsible for basal promoter activity. A 922-bp fragment from -744 to +178 showed the highest level of CAT activity in tire cell lines tested. These data define a functional promoter candidate region for Pkd2. (C) 2000 Academic Press.
AB - Pkd2, the mouse homologue of PKD2, the gene responsible for the second form of autosomal dominant polycystic kidney disease, is highly expressed in fetal and adult mouse tissues. The expression of Pkd2 is developmentally regulated. To begin to dissect out the regulatory mechanism of Pkd2 expression, we characterized the basic features of the gene structure and identified potential cis-regulatory elements of Pkd2 transcription. Pkd2 spans 42 kb with a transcription start site 165 bp upstream of the translation start codon. Exon 1 of Pkd2 is 755 bp long, and the full-length transcript is 5215 bp. The Pkd2 promoter region is GC-rich and lacks a consensus TATA or CCAAT box. Consensus binding sites for the transcription factors Sp-1, NF-1, and Ap-2 lie in the 5' upstream region of Pkd2. The Sp-1 binding site is conserved in 5' upstream sequences of both the mouse and the human genes. The CAT activity of a series of upstream segments from +178 to -2749 was assessed in MDCK, LLCPK1, COS-7, and HEK293 cells. Deletion analysis identified a 409-bp fragment from position -221 to +178 responsible for basal promoter activity. A 922-bp fragment from -744 to +178 showed the highest level of CAT activity in tire cell lines tested. These data define a functional promoter candidate region for Pkd2. (C) 2000 Academic Press.
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U2 - 10.1006/geno.2000.6197
DO - 10.1006/geno.2000.6197
M3 - Article
C2 - 10873385
AN - SCOPUS:0343526351
VL - 66
SP - 305
EP - 312
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 3
ER -