Mettl3-Catalyzed m6A Regulates Histone Modifier and Modification Expression in Self-Renewing Somatic Tissue

The study investigates the role of N6-methyladenosine (m⁶A) in self-renewing somatic tissue by deleting the Mettl3 gene in epidermal progenitors of mice. The absence of Mettl3 leads to significant developmental and self-renewal issues, including disrupted hair follicle morphogenesis and cell adhesion, resulting in oral ulcerations. Mettl3 is shown to facilitate the m⁶A-mediated degradation of mRNAs for key histone modifying enzymes. Without Mettl3, these mRNAs lack m⁶A, leading to increased expression and modifications, causing gene expression abnormalities. The findings highlight the crucial role of Mettl3-catalyzed m⁶A in regulating chromatin modifiers and ensuring proper epithelial development and self-renewal.