A cell-type specific and enhancer-dependent silencer in the regulation of the expression of the human urokinase plasminogen activator gene.
A transcriptional silencer has been identified in the 5' regulatory region of the human urokinase plasminogen activator (uPA) gene. This region is able to block transcription from the human u-PA as well as the rabbit beta-globin promoters in a cell type specific and orientation independent way. The silencer is enhancer dependent and is active in two cell lines (HeLa and CV-1) which produce little if any uPA, but not in the high uPA producer PC3. Silencing activity and enhancer dependence can be separated: the silencing activity has been localized to the DNA fragment -660 to -536, while the enhancer dependence is located in the -536 to -308 fragment. The DNA sequence of the silencer region contains an element that closely resembles the TGF-beta responsive negative element TIE.
Cannio
R
R
Institute of Microbiology, University of Copenhagen, Denmark.
Rennie
P S
PS
Blasi
F
F
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D005914:Globins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010960:Plasminogen Activators / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D012313:RNA / Q000302:isolation & purification; D012045:Regulatory Sequences, Nucleic Acid; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014158:Transcription, Genetic; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
D012313:RNA; D005914:Globins; D004247:DNA; D015719:Single-Strand Specific DNA and RNA Endonucleases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator