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H2AK119ub DUB screen post-heat shock

Wink, Simon (2021) H2AK119ub DUB screen post-heat shock. Research Project 1, Biomedical Sciences.

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Polycomb repressive complex (PRC) 1 and 2 histone modifications H2AK119ub and H3K27me3 together mediate genetic silencing. This silencing is critically important for healthy stem cell biology. Heat shock leads to destabilization of these modifications at different kinetic rates, suggesting enzymatic removal of H2AK119ub. Here we sought to investigate the existence of deubiquitinating enzymes or a potential recruiter ZRF1 via shRNA knockdown screen. Furthermore, we investigated the effect of ZRF1 on Polycomb subunit CBX2 and cell survival. We observed no genes screened here to be responsible, individually or together, for H2AK119ub deubiquitination during heat shock, nor does ZRF1 appear to recruit enzymes involved in this. ZRF1 also does not appear to influence CBX2 behaviour. Further we show that K562 cells are reliant on ZRF1 expression to survive and even more reliant during stress conditions. Our findings show a continued gap-in-knowledge regarding the deubiquitination of H2AK119ub during heat shock, calling for further exploration. We eliminated some potential associations ZRF1 may have had with PRC1. Lastly, we show a reliance on ZRF1 for survival and proliferation, particular during stress.

Item Type: Thesis (Research Project 1)
Supervisor name: Boom, V. van den and Schuringa, J.J.
Degree programme: Biomedical Sciences
Thesis type: Research Project 1
Language: English
Date Deposited: 13 Oct 2021 13:21
Last Modified: 13 Oct 2021 13:21

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