Activation of telomerase rna gene promoter activity by NF-Y, Sp1, and the retinoblastoma protein and repression by Sp3.
Expression of the human telomerase RNA component gene, hTERC is essential for telomerase activity. The hTERC gene is expressed during embryogenesis and then downregulated during normal development, leaving most adult somatic cells devoid of hTERC expression. During oncogenesis, however, hTERC is re-expressed consequently contributing to the unrestricted proliferative capacity of many human cancers. Thus the identification of the molecular basis for the regulation of the telomerase RNA component gene in normal cells and its deregulation in cancer cells is of immediate interest. We have previously cloned the hTERC promoter and in this study have identified several transcription factors that modulate the expression of hTERC. We demonstrate that NF-Y binding to the CCAAT region of the hTERC promoter is essential for promoter activity. Sp1 and the retinoblastoma protein (pRb) are activators of the hTERC promoter and Sp3 is a potent repressor. These factors appear to act in a species-specific manner. Whereas Sp1 and Sp3 act on the human, bovine, and mouse TERC promoters, pRb activates only the human and bovine promoter, and NF-Y is only essential for the human TERC gene.
CRC Department of Medical Oncology, University of Glasgow, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
J Q
JQ
Zhao
R M
RM
Glasspool
S F
SF
Hoare
A
A
Bilsland
I
I
Szatmari
W N
WN
Keith
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002417:Cattle; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006367:HeLa Cells / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000494:pharmacology*; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000494:pharmacology*; D051705:Sp3 Transcription Factor; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic; D014162:Transfection
D023081:CCAAT-Binding Factor; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; C497122:Sp3 protein, mouse; D014157:Transcription Factors; C422952:telomerase RNA; D051705:Sp3 Transcription Factor; D012313:RNA; D019098:Telomerase