6/6 Want the full picture? Check out our preprint, or reach out to any of the amazing authors who made this story possible >> @steinpau.bsky.social, @martinestermann.bsky.social @williamsrepro.bsky.social, Lenka Radonova

www.biorxiv.org/content/10.1...

5/6 The exciting part? This abnormal calcium-induced epigenetic reprogramming can be rescued by adding exogenous lactyl-CoA, which restores global H3K18la and global transcription at the 2-cell stage.

4/6 And guess what? We demonstrated that calcium signals at fertilization function as a metabolic regulator, altering the availability of lactate and lactyl-CoA. This, in turn, affects H3K18la and impairs Pol I-driven EGA.

3/6 The answer came during our MATEbolism Journal Club, where we learned that lactylation acts as a molecular switch, linking metabolism and chromatin remodeling, and that H3K18-lactylation (H3K18la) and RNA pol-I activity are key for EGA and embryo development.

2/6 Using genetic mouse models or ionomycin treatment to increase calcium exposure, we showed that excess calcium leads to high H3K27ac marks but drastically reduces global transcription at the 1-cell and 2-cell embryo stages. But for the longest time, we couldn’t understand HOW!