Almost in all animals, embryonic genome expression remains quiescent until the maternal-to-zygotic transition (MZT). During MZT, thousands of early zygotic genes are transcribed (zygotic genome activation, ZGA), along with the degradation of major maternal components. We previously identified a transcription factor, Zelda, which collectively and specifically activate zygotic genome through recognize the CAGGTAG-related motifs (Liang, et al., 2008). This is the first identified master regulator of ZGA. Extensive analysis of Zelda binding profile from us and others suggested that Zelda binds to thousands of loci, with a pattern correlated to high occupancy of early transcription factors and reduced nucleosome occupancy (Harrison, et al., 2011; Nien, et al., 2011; Sun, et al., 2015). This suggested that, in addition to direct activation, Zelda acts in a way similar to the concept of pioneer factors, which can bind to closed chromatin and regulate chromatin accessibility. However, the underlying molecular mechanism of Zelda remains unclear. Dissection of the functional domains of Zelda protein and identification of Zelda co-factors will help to further understand the dual function (direct activator and pioneer factors) of Zelda.Furthermore, it has been shown that vertebrate embryonic cells undergo a short pluripotent period, coinciding with ZGA (Tadros & Lipshitz, 2009), whereby the chromatin signature is established (Vastenhouw, et al., 2010). However, their relationships require more examination. Interestingly, a group of pluripotency factors, Nanog, Oct4 and SoxB1 family essential for fibroblast reprogramming were implicated to function as pioneer factors in introducing stem cells (Soufi et al., 2012). More recently, the orthologs of these factors were shown to initiate the first wave of ZGA in zebrafish (Lee et al., 2013; Leichsenring et al., 2013). Taken these together, it seems that the strategy of using one or a few factors to globally active early zygotic genome through modifying the chromatin landscapes could be a conserved strategy in ZGA and establishing embryonic pluripotency. In my study, I will test whether Zelda is sufficient to induce pluripotency in fly cells and explore the association between epigenetic modifications and embryonic pluripotency.Specific Aims include: (1) To test whether Zelda is sufficient to induce the pluripotency in Drosophila cells. (2) To dissect Zelda functional domains. (3) To identify potential cofactors of Zelda.
|Effective start/end date||1/08/18 → 31/07/19|
UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):
- zygotic genome activation
- gene regulation
- maternal-to-zygotic transition
- nucleosome occupancy
- embryonic pluripotency
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