An H3K27la-mediated epigenetic pathway programs myofiber type and meat quality in goats

Myofiber type determines meat quality by governing postmortem glycolytic potential and lactate-driven pH decline. However, whether endogenous lactate actively regulates myofiber type through epigenetic signaling remains unknown. Here, we found that histone H3 lysine 27 lactylation (H3K27la), a modification driven by lactate, is a critical regulator of myoblast differentiation. Elevating lactate enhanced differentiation and H3K27la levels in myoblasts. Multi-omics analyses revealed that H3K27la enrichment is associated with transcriptional repression of the member of RAS oncogene family (RAP2C) during goat myoblast differentiation. This inactivation of the RAP2C-ERK-ELK1 signaling axis subsequently upregulates myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF), thereby promoting glycolytic myofiber specification. Our study uncovers a lactate-H3K27la regulatory axis that translates the metabolic state of developing muscle into an epigenetic signal that orchestrates myofiber type, providing profound insights into the early-life programming of myofiber determination and meat quality.