Characterization of the methylation-sensitive promoter of the imprinted ZAC gene supports its role in transient neonatal diabetes mellitus
| Autor: | Céline Fernandez, Joël Bockaert, Barbara Ahr, Deborah J G Mackay, Laurent Journot, Annie Varrault, Eugenia Basyuk, Benoit Bilanges, David O. Robinson |
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| Rok vydání: | 2001 |
| Předmět: |
Tumor suppressor gene
Transcription Genetic Cell Cycle Proteins Biology Transfection Biochemistry Diabetes mellitus genetics Genomic Imprinting medicine Diabetes Mellitus Tumor Cells Cultured Gene silencing Humans Genes Tumor Suppressor Tissue Distribution Gene Silencing Cloning Molecular Promoter Regions Genetic Molecular Biology Alleles Models Genetic Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Infant Newborn Chromosome Mapping Cell Biology Methylation Exons DNA Methylation medicine.disease Molecular biology Introns CpG site Transient neonatal diabetes mellitus DNA methylation Cancer research Trans-Activators Chromosomes Human Pair 6 CpG Islands Genomic imprinting Cell Division Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 276(22) |
| ISSN: | 0021-9258 |
| Popis: | ZAC is a recently isolated zinc finger protein that induces apoptosis and cell cycle arrest. The corresponding gene is imprinted maternally through an unknown mechanism and maps to 6q24-q25, within the minimal interval harboring the gene responsible for transient neonatal diabetes mellitus (TNDM) and a tumor suppressor gene involved in breast cancer. Because of its functional properties, imprinting status, and expression pattern in mammary cell lines and tumors, ZAC is the best candidate so far for both disease conditions. In the present work, we delineated ZAC genomic organization and mapped its transcriptional start site. It is noteworthy that the ZAC promoter localized to the CpG island harboring the methylation imprint associated with TNDM and methylation of this promoter silenced its activity. These data indicate that the methylation mark may have a direct effect on the silencing of the ZAC imprinted allele. Our findings further strengthen the hypothesis that ZAC is the gene responsible for TNDM and suggest a novel mechanism for ZAC inactivation in breast tumors. |
| Databáze: | OpenAIRE |
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