Setdb1, a histone 3 lysine 9 (H3K9) methyltransferase, is a critical epigenetic regulator during various developmental progresses. While distinct functions have been described in diverse tissues and species, the molecular mechanism by which it can carry out such wide range of tasks is poorly understood. Here, I aim to elucidate the roles of Setdb1 in regulating genome organization in mouse stem/progenitor cells, proviral silencing in human melanoma and transcription control in Drosophila germline development. Employing epigenomic tools such as ChIP-‐seq, RNA-‐seq, Hi-‐C and bisulfite sequencing, in addition to mining publically available data, I discovered several novel features of this chromatin modifier. In mESCs, the antagonistic relationship between Setdb1 and CTCF suggests the role of Setdb1 in maintenance of 3D genome architecture by regulating chromatin loop formations. Furthermore, in human melanoma cells, SETDB1 potentially compensates for DNA hypothethylation in repressing repetitive elements. Finally, in Drosophila melanogaster ovaries, dSETDB1 participates in germline specific transcriptional silencing, analogous to its mammalian counterpart. Taken together, this study highlights the distinct molecular mechanisms of Setdb1 to carry out its diverse roles in various cell types by interplaying with other chromatin modifiers.
| Date of Award | 2019 |
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| Original language | English |
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| Awarding Institution | - The Hong Kong University of Science and Technology
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Elucidating the distinct molecular mechanisms of Setdb1
TAM, L. F. (Author). 2019
Student thesis: Master's thesis