Characterization of the ZNF179 promoter: identification of transcription factors that regulate ZNF179 expression during neural differentiation
| Autor: | I-Fang Wang, 王怡方 |
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| Rok vydání: | 2009 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 97 ZNF179, a novel and function uncertain gene, belongs to the RING finger protein family. The expression of ZNF179 was shown to be accompanied with the embryogenesis and sustains high expression level in the adult brain. From the Gene Expression Omnibus (GEO), a public gene expression profiles database, the expression of ZNF179 was significantly decreased in the neurodegenerative diseases such as Huntington’s disease and amyotrophic lateral sclerosis (ALS), indicating expression level of ZNF179 might play functional role in these diseases. Previously, we have demonstrated that the expression of ZNF179 was increased in the retinoic acid-induced neural differentiation of P19 cells, and knockdown of ZNF179 can significantly attenuate neural differentiation. Therefore investigating the molecular mechanism of ZNF179 gene expression can provide useful information in revealing its function in cells. During the neural differentiation process of P19 cells, the expression of many genes can be regulated through the epigenetic controls, such as DNA demethylation. However, the promoter methylation of ZNF179 is consistent during the differentiation process. Next, we analyzed the promoter region of ZNF179 gene, by using various fragments of 5’-upstream region to verify the promoter activity of ZNF179 during P19 cells neural differentiation, the region containing -533/-5 fragment of ZNF179 promtor is sufficient for its transcriptional activity. Meanwhile, several interesting transcription factor binding motifs were predicted, such as Gata2 and Purα. By using site-directed mutagenesis, reporter assay and chromatin immunoprecipitation analysis, we demonstrated that Purα plays an important role in induction of ZNF179 expression during the neural differentiation process of P19 cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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