Transcriptional regulation of the generic promoter III of the rat prolactin receptor gene by C/EBPbeta and Sp1.
Three promoters are operative in the rat prolactin receptor gene as follows: promoter I (PI) and II (PII) are specific for the gonads and liver, respectively, and promoter III (PIII) is common to several tissues. To investigate the mechanisms controlling the activity of promoter III, its regulatory elements and transcription factors were characterized in gonadal and non-gonadal cells. The TATA-less PIII domain was localized to the region -437 to -179 (ATG +1) containing the 5'-flanking region and part of the non-coding first exon. Within the promoter domain, a functional CAAT-box/enhancer binding protein (C/EBP) (-398) and an Sp1 element (-386), which bind C/EBPbeta and Sp1/Sp3, respectively, contribute individually to promoter activation in gonadal and non-gonadal cells. However, significant redundancy was demonstrated between these elements in non-gonadal cells. Additionally, an element within the non-coding exon 1 (-338) is also required for promoter activity. Activation of PIII by the widely expressed Sp1 and C/EBPbeta factors explains its common utilization in multiple tissues. Moreover, whereas the rat and mouse PIII share similar structure and function, the mouse PI lacks the functional SF-1 element and hence is inactive. These findings indicate that promoter III is of central importance in prolactin receptor gene transcription across species.
Hu
Z Z
ZZ
Section on Molecular Endocrinology, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zhuang
L
L
Meng
J
J
Dufau
M L
ML
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006066:Gonads / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011981:Receptors, Prolactin / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011981:Receptors, Prolactin; D016329:Sp1 Transcription Factor