A close link between metabolic methionine pathway and methylation of histone 3 lysine 9 (H3K9)

摘要

Chromatin is structurally remodeled by various posttranslational modifications including acetylation, methylation, phosphorylation, and ubiquitination. Among histone modification, methylation reaction is preceded by utilizing S-adenosylmethionine (SAM) of metabolic methionine pathway as a methyl donor in the cells. To examine how dietary methionine pathway is connected with histone methylation, we have treated methionine metabolites and synthetic analogs on the culturing cells. Most of methionine metabolites had no effect on the cell growth, but synthetic analogs of S-adenosylhomocysteine (SAH) showed cell death-related inhibitory effect. Using western blot analysis, we found that dimethylation of histone 3 lysine 9 (H3K9) but not that of H3K4 or H3K36, was specifically reduced by metabolites treatment. However, methylation of H3K9 (di) was restored by withdrawal of the metabolites. When methionine was deprived from culturing condition, H3K9 (di) methylation be decreased, but restored by treatment of metabolites such as SAM or homocysteine. We also obtained specific reduction of H3K9 by metabolites treatment using the immunostaining analysis. Therefore, we suggest that there is a close link between dietary methionine pathway and methylation of H3K9.