Selenium-induced senescence involves heterochromatin formation

Abstract

Abstract

We have recently shown that selenium compounds can induce a senescence response in a manner depending on ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK), p53 and reactive oxygen species (ROS). To test the hypothesis that the selenium-induced senescence response involves epigenetic changes in senescence-associated heterochromatin foci (SAHF), we determined the expression of histone H3 Lysine 9 trimethylation (H3K9me3), a marker of SAHF, in human primary MRC-5 cells treated with methylseleninic acid (MSeA, 2 μM) for 2 days, followed by a 7-day recovery, in the presence or absence of KU55933 (10 μM), an ATM kinase inhibitor, and NU7026 (10 μM), a DNA-PK kinase inhibitor. Our results showed that MSeA treatment induced the formation of SAHF and H3K9me3 foci. Pre-treatment of the cells with KU55955 or NU7026 resulted in numerous and smaller foci, and they did not co-localize with the MSeA-induced SAHF. These results suggest that the MSeA-induced senescence response involves epigenetic changes of H3K9me3 in a manner depending on ATM and DNA-PK.