Identification and characterization of negative regulatory elements of the human telomerase catalytic subunit (hTERT) gene promoter: possible role of MZF-2 in transcriptional repression of hTERT
| Autor: | Morinobu Takahashi, Kohtaro Fujimoto, Masahiro Takakura, Taro Kanaya, Yasuhide Kitagawa, Satoru Kyo, Masaki Inoue, Hideaki Itoh |
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| Rok vydání: | 2000 |
| Předmět: |
Telomerase
Transcription Genetic Protein subunit Kruppel-Like Transcription Factors Repressor Down-Regulation Biology Response Elements Transfection Article Transcription (biology) Catalytic Domain Consensus Sequence Genetics Tumor Cells Cultured Humans Telomerase reverse transcriptase Gene Silencing RNA Messenger Promoter Regions Genetic Transcription factor neoplasms Zinc finger Binding Sites Base Sequence Reverse Transcriptase Polymerase Chain Reaction Promoter Cell Differentiation Zinc Fingers DNA Molecular biology DNA-Binding Proteins Repressor Proteins enzymes and coenzymes (carbohydrates) embryonic structures Mutation RNA Transcription Factors |
| Zdroj: | Nucleic acids research. 28(13) |
| ISSN: | 1362-4962 |
| Popis: | Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of human telomerase and is a critical determinant of the enzymatic activity of telomerase. Expression of hTERT is known to be regulated mainly at the transcriptional level. In the present study, using transient expression assays, we identified a 400 bp silencer of the hTERT promoter between –776 and –378 upstream of the proximal core promoter. The inhibitory effects of this silencer were enhanced with cellular differentiation. A computer-assisted homology search identified multiple binding motifs for myeloid-specific zinc finger protein 2 (MZF-2) within this region. Mutation introduced in these sites resulted in significant activation of hTERT transcription. Gel shift assays demonstrated that MZF-2 proteins specifically bound to these sites. Overexpression of MZF-2 in cells led to down-regulation of hTERT transcription as well as telomerase activity. These findings suggest that the 400 bp region upstream of the hTERT core promoter that we identified functions as a negative regulatory region and that MZF-2 may be an effector of negative regulation of hTERT. |
| Databáze: | OpenAIRE |
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