ZBTB18-mediated STAT1 transcriptional repression contributes to bovine myogenesis, implying an association with oxidative myofiber formation and beef eating quality

Abstract

Skeletal muscle development, orchestrated by muscle stem cells (MuSCs), is a critical determinant of meat yield and quality in cattle. Transcription factors (TFs) are pivotal regulators of MuSCs fate, yet their specific roles in meat quality remain largely unexplored. In this study, we integrated ATAC-seq and RNA-seq analyses to delineate the chromatin accessibility landscape and transcriptomic dynamics during bovine MuSCs myogenesis, identifying ZBTB18 as a core TF dynamically regulated in this process. ZBTB18 expression was higher in muscles enriched with oxidative myofibers and positively correlated with beef eating quality-related parameters. Functional assays demonstrated that ZBTB18 inhibits MuSCs proliferation while promoting myogenic differentiation, with a specific bias toward oxidative myofiber formation. Mechanistically, we established that ZBTB18 acts as a transcriptional repressor of STAT1. Our findings unveil ZBTB18 as a novel regulator of bovine myogenesis via transcriptional repression of STAT1. Notably, ZBTB18 expression is significantly associated with oxidative myofiber formation and beef eating quality. These findings also provide a strategic target for precision breeding to enhance meat quality in cattle.