8-Chloro-adenosine-induced H3K79me2 Promotes Transcriptional Activation of NBS1 and p21 Genes in Response to DNA Double-stranded Breaks

Methylation of H3K79,including mono,di and trimethyled H3K79(H3K79me1,H3K79me2 and H3K79me3),is one of the landmark modifications associated with euchromatin.However,the roles of methylated H3K79 in gene regulation,DNA damage and repair are unclear.In this study,we showed that the levels of NBS1(a DNA damage response protein),p21(a DNA damage checkpoint protein),and three methylated H3K79 were markedly up-regulated in 8-Cl-Ado-exposed H1299 cells,evidenced by Western blotting.The combination of chromatin immunoprecipitation(ChIP)with real-time quantitative PCR(RT-qPCR)revealed that only H3K79me2 was associated with the NBS1 and p21 promoters,indicating the contribution of H3K79me2,to transcriptional activation of these genes.These results suggest that H3K79me2,but not H3K79me1 and H3K79me3,is involved in the chromatin remodeling associated with the transcription activation of the NBS1 and p21 genes.Induction of H3K79me2 by 8-Cl-Ado in the chromatin surrounding the NBS1 and p21 genes may be a way by that 8-Cl-Ado inhibits tumor cell proliferation.