Abstract: 0bjective To screen valid plasmid targeted to GCN5 among the constructed recombinant plasmids; and to explore the effects of histone acetylizad modification in regulating MSCs differentiation Methods Abstract the constructed plasmids and transfect them into MSCs induced by 5-aza. For 24h, observe MSCs under fluorescence microscope; detect the transfect efficiency by flow cytometry ; detect expression of protein GCN5 by Western-blot; detect the HAT activity by ELISA. Results Transfect efficiency was more than 20%; Expression of protein GCN5 and HAT activity had no difference in group ZJ1 and ZJ2, and had a significant difference in group ZJ3. The HAT activity of experiment group was significantly lower than that of all control groups. Conclusion The inhibitory state of histone acetylation results in plasmid ZJ3 , it can inhibit the differentiation process of MSCs. The results provide data for the clinical application of MSCs transplantation.