Original title: Funkce Zinc-finger proteinu 644 (Zfp644) v myším organismu.
Translated title: Function of Zinc finger protein 644 (Zfp644) in mouse organism.
Authors: Szczerkowska, Katarzyna Izabela ; Sedláček, Radislav (advisor) ; Komrsková, Kateřina (referee) ; Blahoš, Jaroslav (referee)
Document type: Doctoral theses
Year: 2022
Language: eng
Abstract: [eng] [cze]
ZNF644 (Zinc Finger Protein 644) is a C2H2 zinc finger gene encoding a putative transcription regulator, of which a point mutation (S672G) is associated with inherited high myopia in humans. It is also described to be a partner of the G9a/GLP (G9a- euchromatic histone- lysine N-methyltransferase 2, EHMT2; GLP - euchromatic histone-lysine N-methyltransferase 1, EHMT1) complex, known for its essential role in histone methylation, specifically H3K9me1and H3K9me2. It was reported that another transcription factor, WIZ (Widely-Interspaced Zinc Finger-Containing Protein), can bind to this complex and cooperate in gene silencing simultaneously. In order to study Zfp644 impact on myopia, we generated a mouse model, Zfp644S673G that mimics human mutation. In addition, a mouse with a persuasive truncated form of the protein, Zfp644Δ8 was created. Both mouse models went through an examination of retinal function and morphology. Moreover, with use of ultrasonography, different ocular parameters were examined. We conclude, that Zfp644 gene is causative for myopia in mice. Further examinations of Zfp644Δ8 animals show severe symptoms in metabolism and female fertility. To describe the impact of Zfp644 in mouse fertility we performed various experiments including analysis of expression of Zfp644 in reproductive... Gen ZNF644 kóduje transkripční regulátor Zinc Finger Protein 644 patřící do podrodiny Cys2-His2 zinc finger proteinů. Mutace lidskeho ZFN644 (S672G) způsobuje vážnou dědičnou myopii. Výzkum ukázal, že ZFN644 ovlivnujě expresi podřízených genů prostřednictvím interakce s komplexem G9a/GLP (G9a - euchromatic histone-lysine N-methyltransferase 2, EHMT2; GLP - euchromatic histone-lysine N-methyltransferase 1, EHMT1), který hraje významnou roli při methylaci histonů, konkrétně H3Kme1 a H3K9me2. Dále tento komplex může vázat transkripční factor WIZ (Widely-Interspaced Zinc Finger-Containing Protein) a tím současně regulovat umlčení jemu podřízených genů. Abychom mohli studovat dopad mutace ZFP644 na vývoj myopie, vytvořili jsme myší modely, jeden mimikující lidskou mutaci - Zfp644S673G a druhý se zkrácenou formou proteinu Zfp644Δ8 . Oba modely byly podrobeny důkladné vyšetření funkce a morfologie retiny. S využitím ultrasonografie, byly u těchto modelů odhaleny fenotypy v podobě poruchy retiny. Měření potvrdilo spojitost mutace Zfp644 a myopie v obou modelech, navíc byly odhaleny vážné poruchy metabolismu a fertility samic u Zfp644Δ8 modelu. Pro detailnější popis vlivu Zfp644 na plodnost byly provedeny experimenty zahrnujicí analýzu exprese Zfp644 v reprodukčních orgánech, morfometrie vaječníků,...
Keywords: development; epigenetics; fertility; G9a; GLP; histone methylation; mutation; transcription factor; transgenic mouse; vision; WIZ; Zfp644; ZNF644; epigenetika; G9a; GLP; metylace; mutace; plodnost; transgenní myš; vyvoj; WIZ; Zfp644; zinc-finger; ZNF644; zrak

Institution: Charles University Faculties (theses) (web)
Document availability information: Available in the Charles University Digital Repository.
Original record: http://hdl.handle.net/20.500.11956/171339

Permalink: http://www.nusl.cz/ntk/nusl-455950


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Universities and colleges > Public universities > Charles University > Charles University Faculties (theses)
Academic theses (ETDs) > Doctoral theses