Differentiation-dependent and cell-specific regulation of the hIGFBP-1 gene in human endometrium.
We analyzed IGFBP-1 gene promoter activity by transient transfection during the progressive decidualization of human endometrial stromal cells. A time study over a 13-day culture period showed that the promoter activity increased exponentially to > 10(4) fold in cells treated with MPA and RLX correlating with the secretion rate and steady-state mRNA levels of the endogenous gene. Deletion analysis showed that two regions in the IGFBP-1 gene promoter are responsible for the activation of the IGFBP-1 gene. The basal promoter region between -1 and -300 bp contains multiple sections of functional elements homologous either to CRE, PRE, or CCAAT. The major difference of IGFBP-1 gene activation in endometrium and the hepatic system lies in the distal promoter region, between -2.6 and -3.4 kb, which mediates 95% of the total promoter activity derived from -3.3 kb to +68 bp. Functional and binding analysis in the distal promoter region showed that multiple Sp1 elements interacting with a novel Sp3 transcription factor activates the hIGFBP-1 gene promoter.
Tseng
L
L
Department of Obstetrics, Gynecology and Reproductive Medicine, State University of New York at Stony Brook 11794, USA. Ltseng@epo.hsc.sunysb.edu
Gao
J
J
Mazella
J
J
Zhu
H H
HH
Lane
B
B
D002454:Cell Differentiation / Q000235:genetics; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006031:Glycosylation; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis* / Q000235:genetics*; D010766:Phosphorylation; D015533:Transcriptional Activation
D018970:Insulin-Like Growth Factor Binding Protein 1