抄録
In recent years, the covalent modifications of histone tails have emerged as a crucial step in controlling transcription of eukaryotic genes. In this study, we examined the effects of formaldehyde (FA) on histone modifications and the relationship with induction of proto-oncogenes such as c-jun and c-fos. Since inhalation is the primary route for human exposure to FA, the human lung carcinoma A549 cells were utilized as the cell model in the present study. We mainly examined two kinds of histone modifications; 1) phosphorylation of histone H3 at Ser10 and 2) acetylation of histone H3 at Lys9 and Lys14. FA induced phosphorylation of histone H3 at Ser10, which was remarkable at 120 min after the treatment. In contrast, acetylation levels of histone H3 at Lys9 and Lys14, decreased during 10 min to 240 min and increased from 360 min. It has been reported that the increase of phosphorylated histone H3 at Ser10 was due to stimulation of MAPK pathway. JNK inhibitor suppressed the FA-induced phosphorylation, suggesting that activation of JNK pathway contributed to the phosphorylation. By using chromatin immunoprecipitation (ChIP) assay, we revealed a considerable increase in the levels of phosphorylated histone H3 on the c-fos promoter region after treatment with FA. These results suggested that FA could induce chromatin remodeling leading to the altered expression of genes such as proto-oncogene c-fos, which might contribute to carcinogenic effects of FA.
