Methylation of CpGs as a determinant of transcriptional activation at alternative promoters for transforming growth factor-beta3
| Autor: | W B, Archey, M P, Sweet, G C, Alig, B A, Arrick |
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| Rok vydání: | 1999 |
| Předmět: |
Transcription
Genetic Breast Neoplasms Sarcoma DNA Neoplasm DNA Methylation Cell Line Neoplasm Proteins Gene Expression Regulation Neoplastic Gene Expression Regulation Organ Specificity Transforming Growth Factor beta Tumor Cells Cultured Humans CpG Islands Female RNA Messenger Promoter Regions Genetic |
| Zdroj: | Cancer research. 59(10) |
| ISSN: | 0008-5472 |
| Popis: | The human transforming growth factor-beta3 (TGF-beta3) gene has a typical CpG island, the core of which is centered just upstream of its principle promoter. Activation of an alternative downstream promoter, leading to the production of a truncated mRNA lacking the portion of the 5' noncoding region responsible for translational inhibition of TGF-beta3 mRNA, is only evident in breast cancer cells. We compared the methylation status of genomic DNA isolated from a panel of breast (SKBR-3 and T47-D) and non-breast cancer (HT-1080, A673, and A375) cell lines by sequencing sodium metabisulfite-treated DNA. In all cell lines, the core of the TGF-beta3 CpG island was predominantly unmethylated, irrespective of promoter usage associated with that cell line. In contrast, we observed a marked difference in methylation at 19 CpG sites immediately flanking and downstream of the alternative promoter's transcription initiation site. Specifically, the non-breast cancer cell lines exhibited nearly complete methylation of these CpG sites, whereas in the breast cancer cell lines, these CpGs were predominantly unmethylated. Our data support the hypothesis that methylation of a limited number of CpGs at the periphery of an otherwise unmethylated CpG island underlies the transcriptional repression of the downstream promoter in non-breast cancer cells, thereby serving to regulate the use of alternative promoters for TGF-beta3. |
| Databáze: | OpenAIRE |
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