Wound-induced regeneration involves two spectutive developmental processes: 1) differentiated cells at the wound site rapidly reprogram their fates to become undifferentiated;2) the undifferentiated stem-cell-like cells re-differentiate to generate new tissues or organs to restore the body plan.It remains intriguing how these two distinct processes are achieved by orchestrated cell fate reprogramming and re-acquisition.Epigenetic mechanisms contribute to cell differentiation and fate reprogramming by changing the chromatin state to regulate globally the transcription of a large set of genes.Genes are packed on nucleosomes which are made of histone proteins.Histone variants play important roles in genome-wide transcriptional regulation.It is expected that dynamic changes in histone variant H3.3 profiles facilitate the extensive remodeling of the transcriptome that occurs during cell differentiation.Here we report our comparative studies in Arabidopsis thaliana and Hydra, combining approaches in cell biology, molecular biology, genomics and bio-imaging to address the contribution of histone H3 variants to epigenetic cell fate reprogramming in wound-induced regeneration.