Acetylation of
histone and non-
histone proteins by
histone acetyltransferases plays a pivotal role in the expression of proinflammatory genes. Given the importance of dietary
selenium in mitigating
inflammation, we hypothesized that
selenium supplementation may regulate inflammatory gene expression at the epigenetic level. The effect of
selenium towards
histone acetylation was examined in both in vitro and in vivo models of
inflammation by
chromatin immunoprecipitation assays and immunoblotting. Our results indicated that
selenium supplementation, as
selenite, decreased acetylation of
histone H4 at K12 and K16 in COX-2 and TNFα promoters, and of the p65 subunit of the redox sensitive
transcription factor NFκB in primary and immortalized macrophages. On the other hand,
selenomethionine had a much weaker effect.
Selenite treatment of HIV-1-infected human monocytes also significantly decreased the acetylation of H4 at K12 and K16 on the HIV-1 promoter, supporting the down-regulation of proviral expression by
selenium. A similar decrease in
histone acetylation was also seen in the colonic extracts of mice treated with
dextran sodium sulfate that correlated well with the levels of
selenium in the diet. Bone-marrow-derived macrophages from Trsp(fl/fl)Cre(LysM) mice that lack expression of
selenoproteins in macrophages confirmed the important role of
selenoproteins in the inhibition of
histone H4 acetylation. Our studies suggest that the ability of
selenoproteins to skew the metabolism of
arachidonic acid contributes, in part, to their ability to inhibit
histone acetylation. In summary, our studies suggest a new role for
selenoproteins in the epigenetic modulation of proinflammatory genes.