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Potenciální vliv tkáňově specifických transkripčních faktorů na expresi metalothioneinů
Michálková, Nikola
Metallothioneins represent a group of intracellular proteins capable of binding metal ions, and their function includes the regulation of cellular levels of these metal ions. Transcription factors are central regulators of gene expression and play an important role in regulating the expression of metallothionein genes, which represents the basic mechanism for the cellular response to changes in metal ion levels. Although transcription factors that bind to the promoter regions of metallothioneins are known, their role in inducing the expression of metallothionein genes is far from clear. The subject of this thesis was the induction of gene expression of metallothioneins by zinc ions in HUH7 (hepatocellular carcinoma) and T47D (breast cancer) cell lines, and the subsequent analysis of gene expression of selected transcription factors. The selection of transcription factors was based on TF ChIP-seq analysis of ENCODE database. For the experimental part, the transcription factors FOXA1, FOXA2, HNF4A, and HNF4G were chosen, whose high levels are typical for liver tissue. Furthermore, gene expression of the ubiquitinated transcription factors JUND, NR3C1, RXRA, STAT3, SP1, and MTF1 was monitored. Statistically significant changes in gene expression (RT-qPCR) after short-term exposure (4-6 h) to 100 μM ZnSO4 were observed for FOXA1, JUND, and MTF1. In the case of FOXA1, a decrease in gene expression was observed in both tumor lines compared to the control, whereas an increase in expression was observed in JUND and MTF1 after ZnSO4 treatment. In the case of MTF1, a significant increase was observed only in the HUH7 tumor line. The results show that, in addition to the validated zinc-sensitive transcription factor MTF1, the transcription factors FOXA1 and JUND could also be involved in the regulation of metallothionein gene expression. FOXA1 could represent a potential repressor and inducer of JUND metallothionein expression in response to increased exposure to zinc ions.
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