Background:The FACT complex reorganizes nucleosomes and functions in DNA replication, transcription, and DNA repair. Results: Myogenin interacts with FACT, which is required for histone depletion at promoters and initiation of gene expression. Conclusion: Myogenin recruits the FACT complex to muscle-specific genes where FACT depletes nucleosomes at promoters, thus facilitating gene expression. Significance: The recruitment of FACT by myogenin is crucial to activate myogenin-dependent genes.