Selenium's Epigenetic Modulation of Proinflammatory Genes Revealed

Selenium has long been recognized as an essential nutrient, particularly in its role in mitigating inflammation. Recent research published in the Journal of Nutritional Biochemistry has shed new light on the molecular mechanisms by which selenium exerts its anti-inflammatory effects, revealing a novel role for selenoproteins in the epigenetic regulation of proinflammatory genes.

Key Takeaways:

• Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of proinflammatory genes.
• Selenium supplementation, particularly in the form of selenite, has been shown to decrease acetylation of histone H4 at K12 and K16 in COX-2 and TNF alpha promoters, and of the p65 subunit of the redox sensitive transcription factor NF kappa B in primary and immortalized macrophages.
• 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.
• The ability of selenoproteins to skew the metabolism of arachidonic acid contributes, in part, to their ability to inhibit histone acetylation.

Statistics:

• 26% decrease in histone H4 acetylation at K12 and K16 in COX-2 and TNF alpha promoters in selenite-treated macrophages.
• 30% decrease in histone H4 acetylation at K12 and K16 on the HIV-1 promoter in selenite-treated HIV-1-infected human monocytes.
• 25% decrease in histone H4 acetylation in colonic extracts of mice treated with dextran sodium sulfate.

Sources:

• Journal of Nutritional Biochemistry: 26(2): 138-145, 2015.
• Elsevier Science Inc: 360 Park Ave South, New York, NY 10010-1710, USA. (www.elsevier.com)