Please use this identifier to cite or link to this item: https://doi.org/10.1093/nar/gky659
Title: TIP60 represses activation of endogenous retroviral elements
Authors: Rajagopalan, D. 
Tirado-Magallanes, R. 
Bhatia, S.S.
Teo, W.S. 
Sian, S. 
Hora, S.
Lee, K.K. 
Zhang, Y. 
Jadhav, S.P. 
Wu, Y.
Gan, Y.-H. 
Karnani, N. 
Benoukraf, T. 
Jha, S. 
Issue Date: 2018
Publisher: Oxford University Press
Citation: Rajagopalan, D., Tirado-Magallanes, R., Bhatia, S.S., Teo, W.S., Sian, S., Hora, S., Lee, K.K., Zhang, Y., Jadhav, S.P., Wu, Y., Gan, Y.-H., Karnani, N., Benoukraf, T., Jha, S. (2018). TIP60 represses activation of endogenous retroviral elements. Nucleic Acids Research 46 (18) : 9456-9470. ScholarBank@NUS Repository. https://doi.org/10.1093/nar/gky659
Rights: Attribution-NonCommercial 4.0 International
Abstract: TIP60 is a lysine acetyltransferase and is known to be a haplo-insufficient tumor suppressor. TIP60 downregulation is an early event in tumorigenesis which has been observed in several cancer types including breast and colorectal cancers. However, the mechanism by which it regulates tumor progression is not well understood. In this study, we identified the role of TIP60 in the silencing of endogenous retroviral elements (ERVs). TIP60-mediated silencing of ERVs is dependent on BRD4. TIP60 and BRD4 positively regulate the expression of enzymes, SUV39H1 and SETDB1 and thereby, the global H3K9 trimethylation (H3K9me3) level. In colorectal cancer, we found that the loss of TIP60 de-represses retrotransposon elements genome-wide, which in turn activate the cellular response to pathogens, mediated by STING, culminating in an induction of Interferon Regulatory Factor 7 (IRF7) and associated inflammatory response. In summary, this study has identified a unique mechanism of ERV regulation in cancer cells mediated by TIP60 and BRD4 through regulation of histone H3 K9 trimethylation, and a new tumor suppressive role of TIP60 in vivo. © The Author(s) 2018.
Source Title: Nucleic Acids Research
URI: https://scholarbank.nus.edu.sg/handle/10635/210921
ISSN: 03051048
DOI: 10.1093/nar/gky659
Rights: Attribution-NonCommercial 4.0 International
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