Early lineage-specific master regulators are essential for the specification of cell types. However, once cells are committed to a specific fate, it is critical to restrict the activity of such factors to enable differentiation. To date, it remains unclear how these factors are silenced. Using the Drosophila mesoderm as a model and a comparative genomic approach, we identify the Hox transcription factor Ultrabithorax (Ubx) to be critical for the repression of the master regulator Twist. Mesoderm-specific Ubx loss-of-function experiments using CRISPR-Cas9 and overexpression studies demonstrate that Ubx majorly impacts twist transcription. A mechanistic analysis reveals that Ubx requires the NK-homeodomain protein Tinman to bind to the twist promoter. Furthermore, we find these factor interactions to be critical for silencing by recruiting the Polycomb DNA binding protein Pleiohomeotic. Altogether, our data reveal that Ubx is a critical player in mediating the silencing of Twist, which is crucial for coordinated muscle differentiation.

早期谱系特定的主调节器对于细胞类型的规范至关重要。然而，一旦细胞被赋予特定的命运，就必须限制这些因子的活性以实现分化。迄今为止，尚不清楚这些因素是如何被压制的。使用果蝇中胚层作为模型和比较基因组方法，我们确定 Hox 转录因子 Ultrabithorax (Ubx) 对抑制主调节器 Twist 至关重要。使用 CRISPR-Cas9 和过表达研究的中胚层特异性 Ubx 功能丧失实验表明 Ubx 主要影响扭曲转录。机制分析表明 Ubx 需要 NK 同源域蛋白 Tinman 与扭曲结合发起人。此外，我们发现这些因子相互作用对于通过招募 Polycomb DNA 结合蛋白 Pleiohomeotic 进行沉默至关重要。总而言之，我们的数据显示 Ubx 是调解 Twist 沉默的关键参与者，这对于协调肌肉分化至关重要。