TY - JOUR
T1 - Cloning and characterization of the promoter region of the mouse frizzled-related protein 4 gene
AU - Wai Wong, Vincent Kam
AU - Ping Yam, Judy Wai
AU - Hsiao, W. L.Wendy
N1 - Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Frizzled-related protein (Frp) is a newly identified family of secreted proteins involved in the Wnt signaling pathway. To date, little is known about the underlying mechanisms regulating Frp expression. In this study the promoter region of mouse frizzled related protein 4 (sFrp4) gene was cloned, sequenced, and analyzed using transient reporter assays along with site-directed mutagenesis. Two clusters of cis-acting elements, STAT3/Lyf-1/MZF1 (site 1) and C/EBP-β/ GATA-1/CREB (site 2) located in the promoter region from - 238 to - 144 were found to be essential for the promoter activity of sFrp4. In addition to sites 1 and 2, putative transcriptional factor binding sites for TFIID, SP1/GC and ATF/CREB exhibited positive, while the site for NRSE exhibited negative regulatory functions, as determined by the alkaline phosphatase activities of the reporter assay. We also demonstrate that the ATF/CREB site may cooperatively interact with the NRSF-like element in regulating sFrp4 promoter activity. The data of our study, which is the first promoter analysis of mouse Frp genes, provide the basis for understanding the functions and the regulation of Frp and its role in regulating Wnt signals.
AB - Frizzled-related protein (Frp) is a newly identified family of secreted proteins involved in the Wnt signaling pathway. To date, little is known about the underlying mechanisms regulating Frp expression. In this study the promoter region of mouse frizzled related protein 4 (sFrp4) gene was cloned, sequenced, and analyzed using transient reporter assays along with site-directed mutagenesis. Two clusters of cis-acting elements, STAT3/Lyf-1/MZF1 (site 1) and C/EBP-β/ GATA-1/CREB (site 2) located in the promoter region from - 238 to - 144 were found to be essential for the promoter activity of sFrp4. In addition to sites 1 and 2, putative transcriptional factor binding sites for TFIID, SP1/GC and ATF/CREB exhibited positive, while the site for NRSE exhibited negative regulatory functions, as determined by the alkaline phosphatase activities of the reporter assay. We also demonstrate that the ATF/CREB site may cooperatively interact with the NRSF-like element in regulating sFrp4 promoter activity. The data of our study, which is the first promoter analysis of mouse Frp genes, provide the basis for understanding the functions and the regulation of Frp and its role in regulating Wnt signals.
KW - cAMP responsive element binding protein
KW - Frizzled-related protein
KW - Neuron-restrictive silencer element
UR - http://www.scopus.com/inward/record.url?scp=0141626773&partnerID=8YFLogxK
U2 - 10.1515/BC.2003.127
DO - 10.1515/BC.2003.127
M3 - Journal article
C2 - 12974383
AN - SCOPUS:0141626773
SN - 1431-6730
VL - 384
SP - 1147
EP - 1154
JO - Biological Chemistry
JF - Biological Chemistry
IS - 8
ER -