Six1 orchestrates tongue muscle differentiation by modulating core myogenic transcription factors [CUT&Tag]

In vitro studies in C2C12 cells further demonstrated that Six1 knockdown impaired both cell proliferation and differentiation, as evidenced by reduced expression of myogenic genes, such as Pax7, Myog, and Myf6, as well as diminished cell viability and proliferation. Moreover, CUT&Tag analysis identified 13,454 SIX1-binding peaks in the genome, with SIX1 directly binding to the promoters of key myogenic factors, including Myf5, Myod, and Mylpf.

Epigenetic modifications, such as altered H3K27Ac binding, were also observed, suggesting that Six1 regulates myogenic differentiation through chromatin remodeling. These findings establish SIX1 as a critical regulator of tongue muscle differentiation and suggest its potential involvement in congenital myopathies and craniofacial disorders. Understanding the molecular mechanisms by which Six1 regulates muscle development may provide therapeutic insights into improving muscle regeneration and function in clinical settings.