Multiomics integration uncovers metabolic control of H3K27ac in bovine inner cell masses†

The epigenetic reprogramming that occurs during the early stages of embryonic development has been described as crucial for the initial events of cell specification and differentiation, with possible long-term consequences to the offspring. This investigation explores the link between pyruvate metabolism and epigenetic regulation by culturing bovine embryos from Day 5 in the presence of sodium dichloroacetate (DCA), an organic acid that enhances the conversion of pyruvate to acetyl-CoA, and sodium iodoacetate (IA), which inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to the inhibition of glycolysis. Both treatments led to changes in the levels of H3K27 acetylation as well as their resulting binding patterns across the chromatin in the inner cell masses of blastocysts. An integrative analysis was performed between the molecular data and the results of chromatin state for H3K27ac. DCA led to a more robust association with biological processes related to lipid metabolism, while IA presented a higher binding activity linked to processes such as apoptosis and catabolism. The results discussed here corroborate previous evidence of the relationship between energy metabolism and epigenetic reprogramming in preimplantation bovine embryos, pointing to H3K27ac as an important mark for the immediate response of embryos to environmental changes in culture systems.