Interaction mechanisms of epigenetic integrator UHRF1 with TIP60 acetyltransferase

Abstract : UHRF1 is a nuclear protein maintaining and regulating the epigenome of cells. Its promotes proliferation and is found upregulated in most of cancers. TIP60 is one of the important interacting partner of UHRF1 and is involved in chromatin remodeling and transcriptional regulation through its acetyltransferase activity. Together they regulate the stability and activity of other proteins such as DNMT1 and p53. The aim of this thesis was to explore the mechanism of interaction between UHRF1 and TIP60 by visualizing this interaction in cells. Fluorescent lifetime imaging microscopy and other molecular biology techniques were employed for this purpose. Results of this study showed that UHRF1 interacts directly to the MYST domain of TIP60 and this interaction prevails in the S-phase of cell cycle. Both proteins also showed a similar response to DNA damage predicting a coherence in their function in DNA repair mechanism. Overexpression of TIP60 also downregulated UHRF1 and DNMT1 and induced apoptosis in cells suggesting a role of TIP60 in regulation of oncogenic functions of UHRF1.
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Waseem Ashraf. Interaction mechanisms of epigenetic integrator UHRF1 with TIP60 acetyltransferase. Pharmacology. Université de Strasbourg, 2018. English. ⟨NNT : 2018STRAJ078⟩. ⟨tel-02144590v1⟩

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