Summary S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) link one-carbon metabolism to methylation status. However it is unknown whether regulation of SAM and SAH by nutrient availability can be directly sensed to alter the kinetics of key histone methylation marks. We provide evidence that the status of methionine metabolism is sufficient to determine levels of histone methylation by modulating SAM and SAH. This dynamic interaction led to rapid changes in H3K4me3, altered gene transcription, provided feedback regulation to one-carbon metabolism and could be fully recovered upon restoration of methionine. Modulation of methionine in diet led to changes in metabolism and histone methylation in liver. In humans, methionine variability in fasting serum was commensurate with concentrations needed for these dynamics and could be partly explained by diet. Together these findings demonstrate that flux through methionine metabolism and the sensing of methionine availability may allow for direct communication to the chromatin state in cells.

PYY is characteristically considered an appetite hormone with identified roles in metabolism, inflammation, and proliferation. The expression of PYY and its receptors has been demonstrated in the skeletal muscle; however, the role of PYY in the skeletal muscle is unknown.ObjectiveTo investigate the role of PYY on proliferating and differentiating/differentiated skeletal myoblasts and to determine the effect of PYY on inflammatory and metabolic signaling pathways.MethodsExpression of the PYY gene was determined in cultured murine C2C12 cells incubated in growth or differentiation media (GM and DM, respectively) using quantitative PCR. Additionally, changes in proteins of interest were determined from C2C12 cells that were cultured in DM for 96 h then switched to DM containing 0.1 mM palmitate for 72 h, followed by exposure to 500 pM murine PYY3‐36 for 6 h prior to lysis.ResultsPYY gene expression, which was identified in proliferating C2C12 cells, decreased in differentiating cells. Relative to myotubes that received only palmitate, the presence of PYY decreased phosphorylation of STAT3 (signal transducer and activator of transcription 3) serine‐727 (‐37%, p = 0.03) and tyrosine‐705 (‐33%, p = 0.01). There was no change in the total STAT3 protein, the ratio of phospho‐STAT3 to total STAT3, or NF‐kB‐p65 levels.ConclusionsThese results indicate that the PYY gene is not only detectable in mouse myoblasts, but it also changes with different physiological states (i.e. proliferating vs. differentiating). Additionally, PYY appears to play a role in skeletal muscle STAT3 signaling. Follow‐up research is necessary to confirm these results and identify downstream targets of PYY through the STAT3 pathway and functional outcomes. Support: NIDDK P30DK056336