Tissue-Specific Expression of Estrogen Receptor 1 Is Regulated by DNA Methylation in a T-DMR
| Autor: | Ryo Maekawa, Takuya Kajimura, Shun Sato, Hiromi Asada, Yoshiaki Yamagata, Shigeru Yamamoto, Hiroshi Tamura, Kosuke Jozaki, Norihiro Sugino, Isao Tamura, Maki Okada, Lifa Lee |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Breast Neoplasms Histones 03 medical and health sciences Endocrinology Epigenetics of physical exercise Genes Reporter Transcription (biology) Humans RNA Messenger Promoter Regions Genetic Molecular Biology Transcription factor Original Research Regulation of gene expression Base Sequence biology Estrogen Receptor alpha Promoter Exons General Medicine DNA Methylation Molecular biology Gene Expression Regulation Neoplastic body regions 030104 developmental biology Histone Organ Specificity embryonic structures DNA methylation MCF-7 Cells biology.protein Female Protein Processing Post-Translational Estrogen receptor alpha Protein Binding Transcription Factors |
| Zdroj: | Molecular Endocrinology. 30:335-347 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | The mechanism controlling tissue-specific expression of estrogen receptor 1 (ESR1) is unclear. In other genes, DNA methylation of a region called the tissue-dependent and differentially methylated region (T-DMR) has been associated with tissue-specific gene expression. This study investigated whether human ESR1 has a T-DMR and whether DNA methylation of the T-DMR regulates its expression. ESR1 expression was tissue-specific, being high in the endometrium and mammary gland and low/nil in the placenta and skin. Therefore, DNA methylation profiles of the promoter of ESR1 were analyzed in these tissues and in breast cancer tissues. In all of the normal tissues, the proximal promoter regions were unmethylated. On the other hand, the distal regions (T-DMR) were unmethylated in the endometrium and mammary gland, but were moderately methylated and hypermethylated in the placenta and skin, respectively. T-DMR-methylated reporter assay was performed to examine whether DNA methylation at the T-DMR suppresses ESR1 transcription. T-DMR, but not the promoter region, had transcriptional activities and DNA methylation of the T-DMR suppressed ESR1 transcription. Early growth response protein 1 was shown to be a possible transcription factor to bind the T-DMR and up-regulate ESR1 expression. ESR1 has several upstream exons, and each upstream exon, Exon-A/Exon-B/Exon-C, had its own T-DMR. In some breast cancer cases and breast cancer cell lines, ESR1 expression was not regulated by DNA methylation at T-DMR as it is in normal tissues. In conclusion, ESR1 has a T-DMR. DNA methylation status at the T-DMR is involved in tissue-specific ESR1 expression in normal tissues but not always in breast cancer. |
| Databáze: | OpenAIRE |
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