Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021
Erindi/veggspjald / Talk/poster E76
Höfundar / Authors: Hong Nhung Vu (1) , Ramile Dilshat (2), and Eiríkur Steingrímsson(3)
Starfsvettvangur / Affiliations: Faculty of Medicine, School of Health Sciences, University of Iceland
Kynnir / Presenter: Hong Nhung Vu (nhv2@hi.is)
MITF is known as an essential regulator of melanocyte specification, melanoma cell proliferation, invasion, and drug resistance. The major changes in gene expression upon MITF loss suggests that it might be involved in regulating of epigenetic modifiers to reshape the melanoma chromatin state. In line with this, the histone methyl transferase PRDM7 which is primarily expressed in melanoma was observed to be significantly and possitively correlated with MITF. However, the biological role of PRDM7 remains uncharacterized. Therefore, we have used KD and KO studies to characterize the functional roles of PRDM7 in melanoma. Although the depletion of PRDM7 did not affect expression of the MITF mRNA, MITF protein expression was significant reduced in PRDM7-KO and KD cells, suggesting that PRDM7 affects protein stability or expression. PRDM7-KO cells proliferate slowly and their morphology was altered compared to the control cells. Similar changes were observed upon MITF-KO. Consistent with this, RNA-sequencing showed that the PRDM7-KO cells were enriched for genes involved in extracellular matrix and structure organization as well as EMT genes signature. The same pathways were also enriched upon MITF-KD and KO. Interestingly, the depletion of PRDM7 leads to a massive loss of the repressive histone marks H3K9me3 and H3K27me3 in melanoma cells. Our results suggest that MITF and PRDM7 regulate each other’s expression and are involved in reshaping the chromatin state in melanoma.