Characterization of the Epigenetic Regulation of Mouse Hic1 Gene
| Autor: | Mei-I Chung, 鍾美儀 |
|---|---|
| Rok vydání: | 2005 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 93 Epigenetics is the study of heritable changes in gene expression that are not mediated at the DNA sequence level. The human and mouse HIC1 (hypermethylated in cancer-1) genes are composed of two alternative transcripts, both of which have a large coding exon 2 spliced to alternative exon 1a or exon 1b. The dense methylation of HIC1 has shown to result in the gene inactivation in tumors. However, the detail mechanisms involved in the HIC1 regulation in normal cells are still unclear. We used mouse brain and liver tissues and cell lines to study the epigenetic regulation of Hic1 gene. The exon 1a-containing transcript was observed in all samples. In NIH-3T3 cells, the promoter region of exon 1a showed DNA hypomethylation and histone acetylation. There is a methylation boundary at 5’ regulatory region of exon 1a and we found a CTCF binding site on this boundary region. CTCF may play an important role to protect exon 1a promoter region from DNA methylation. In addition, the further 5’ region of exon 1a with different methylation patterns in tissues and cells was also identified to contain regulatory elements. The exon 1b-containing transcript also exists in the NIH-3T3 cells and mouse brain and liver tissues. However, the DNA methylation patterns of exon 1b and its 5’ regulatory region are partial or hypermethylated. Despite DNA methylation regulation, the mechanisms that regulate exon 1b-containing transcript were not clear. We suggested that the region between exon 1b and exon 2 which showed promoter activity may regulate this transcript expression. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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