| Summary: | 碩士 === 國立中興大學 === 分子生物學研究所 === 103 === PAX3 plays a critical role in the regulation of gene expression and in the maintenance pericentromeric heterochromatin (PH). Lose DNA binding ability of PAX3 Missense mutations in homeodomain (HD) are associated with Waardenburg syndrome (WS). However, the mechanism of PAX3 WS effect the PAX3 in gene regulation and PAX3 on PH are not clear. In order to find the evidence of PAX3 mutants in gene regulation, we found that PAX3 mutants changed histone modifiers, including SIRT6, JMJD2A and G9a, by immunofluorescence. Furthermore, Co-IP results showed that PAX3 mutants strongly interacted with these modifiers. Moreover, we found that PAX3 mutants derepressed PAX3-target genes MITF. Also, We using melanin content assay, found that PAX3 decreased endogenous melanin, but PAX3 (R271G) don’t. On the other hands, we investigated the mechanism of PAX3 mutants effect PAX3 on PH. Here, we found that PAX3 mutants are not on PH. Then, we found that PAX3 mutants lost PAX3 on PH. These results indicate that: (1) PAX3 mutants sequestered histone modifiers, leading to a decrease in the association between wild type PAX3 and histone modifiers. This mechanism causes derepression of PAX3 target gene. (2) PAX3 mutants causes PAX3 lost on PH.
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