Regulacja epigenetyczna a potencjał regeneracyjny ssaków. Badania globalnych profili metylacji w tkankach dorosłej myszy MRL/MpJ i w sercach noworodków myszy C57BL/6J. - Publication - Bridge of Knowledge

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Regulacja epigenetyczna a potencjał regeneracyjny ssaków. Badania globalnych profili metylacji w tkankach dorosłej myszy MRL/MpJ i w sercach noworodków myszy C57BL/6J.

Abstract

W pracy tej otrzymano genomowe profile metylacji DNA dla dwóch modeli regeneracji u ssaków: (i) dorosłej myszy MRL/MpJ, która jest zdolna do zamykania otworów w małżowinie usznej oraz wykazuje podwyższone zdolności regeneracyjne w wielu innych narządach oraz (ii) sercach noworodków myszy, u których zachodzi regeneracja rozległych uszkodzeń lewej komory serca. Zidentyfikowano szereg odmiennie metylowanych regionów DNA, regionów DMR, pomiędzy myszą MRL/MpJ oraz szczepami kontrolnymi C57BL/6J i BALB/c w różnych tkankach: szpiku kostnym, śledzionie, wątrobie, sercu i małżowinie usznej pochodzących od niezranionych zwierząt. W małżowinie usznej, geny znalezione w sąsiedztwie regionów DMR były związane z procesami wpływającymi na regenerację, takimi jak tworzenie przednio-tylnego wzorca ekspresji genów, stan zapalny i apoptoza. Regiony promotorowe tych genów posiadały miejsca wiązana dla czynnika transkrypcyjnego Smad1, należącego do szlaku sygnałowego Tgfβ/Bmp. Ponadto wiele z tych genów było położone w sąsiedztwie loci cechy ilościowej zdolności do zamykania otworów w uszach. W modelu serca noworodków myszy zidentyfikowano regiony DMR wyróżniające profile metylacji DNA w dniu 1, kiedy obserwowana jest zdolność do regeneracji, i późniejszymi stadiami: dniem 7, 2 oraz 8 tygodniem, kiedy zdolność ta zanika. Geny związane z regionami DMR odpowiedzialne były za rozwój serca oraz tworzenie przednio-tylnego wzorca ekspresji genów. W porównaniu z dniem 1, w dniu siódmym zaobserwowano przeważającą liczbę regionów DMR, w których nastąpił wzrost poziomu metylacji DNA. Analiza bioinformatyczna wyłoniła potencjalne czynniki transkrypcyjnej regulacji, którymi są, zaangażowane w morfogenezę serca Mef2c, Nr2f2, Tead4 oraz Mfsd6l, o funkcji bliżej nieznanej, mające miejsca wiązania w pobliżu odpowiednio około 25% i 50% z 929 regionów DMR.

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Category:
Thesis, nostrification
Type:
praca doktorska pracowników zatrudnionych w PG oraz studentów studium doktoranckiego
Language:
Polish
Publication year:
2016
Bibliography: test
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  2. Wykres rozrzutu prezentujący zmiany obserwowane pomiędzy DMR a poziomem ekspresji genu. open in new tab
  3. Przykładowe geny, których zmiana w poziomie ekspresji została powiązana ze zmianą metylacji DNA. open in new tab
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