TY - JOUR TI - TRAIN (Transcription of Repeats Activates INterferon) in response to chromatin destabilization induced by small molecules in mammalian cells AU - Leonova, Katerina AU - Safina, Alfiya AU - Nesher, Elimelech AU - Sandlesh, Poorva AU - Pratt, Rachel AU - Burkhart, Catherine AU - Lipchick, Brittany AU - Gitlin, Ilya AU - Frangou, Costakis AU - Koman, Igor AU - Wang, Jianmin AU - Kirsanov, Kirill AU - Yakubovskaya, Marianna G AU - Gudkov, Andrei V AU - Gurova, Katerina A2 - Espinosa, Joaquín M VL - 7 PY - 2018 DA - 2018/02/05 SP - e30842 C1 - eLife 2018;7:e30842 DO - 10.7554/eLife.30842 UR - https://doi.org/10.7554/eLife.30842 AB - Cellular responses to the loss of genomic stability are well-established, while how mammalian cells respond to chromatin destabilization is largely unknown. We previously found that DNA demethylation on p53-deficient background leads to transcription of repetitive heterochromatin elements, followed by an interferon response, a phenomenon we named TRAIN (Transcription of Repeats Activates INterferon). Here, we report that curaxin, an anticancer small molecule, destabilizing nucleosomes via disruption of histone/DNA interactions, also induces TRAIN. Furthermore, curaxin inhibits oncogene-induced transformation and tumor growth in mice in an interferon-dependent manner, suggesting that anticancer activity of curaxin, previously attributed to p53-activation and NF-kappaB-inhibition, may also involve induction of interferon response to epigenetic derepression of the cellular ‘repeatome’. Moreover, we observed that another type of drugs decondensing chromatin, HDAC inhibitor, also induces TRAIN. Thus, we proposed that TRAIN may be one of the mechanisms ensuring epigenetic integrity of mammalian cells via elimination of cells with desilenced chromatin. KW - chromatin KW - TRAIN KW - CBL0137 KW - nucleosome KW - curaxin KW - interferons JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -