Master regulatory transcription factors cooperate in networks to shepherd cells through organogenesis. In the Drosophila eye, a collection of master control proteins known as the retinal determination gene network (RDGN) switches the direction and targets of its output to choreograph developmental transitions, but the molecular partners that enable such regulatory flexibility are not known. We recently showed that two RDGN members, Eyes absent (Eya) and Sine oculis (So), promote exit from the terminal cell cycle known as the second mitotic wave (SMW) to permit differentiation. A search for co-factors identified the ubiquitously expressed Combgap (Cg) as a novel transcriptional partner that impedes cell cycle exit and interferes with Eya-So activity specifically in this context. Here, we argue that Cg acts as a flexible transcriptional platform that contributes to numerous gene expression outcomes by a variety of mechanisms. For example, Cg provides repressive activities that dampen Eya-So output, but not by recruiting Polycomb chromatin-remodeling complexes as it does in other contexts. We propose that master regulators depend on both specifically expressed co-factors that assemble the combinatorial code and broadly expressed partners like Cg that recruit the diverse molecular activities needed to appropriately regulate their target enhancers.

主调节转录因子通过器官发生在网络中与牧羊细胞合作。在果蝇中眼中，称为视网膜测定基因网络（RDGN）的一组主控制蛋白将其输出的方向和目标切换到了编排器的发育过渡，但是实现这种调节灵活性的分子伴侣尚不清楚。我们最近显示，两个RDGN成员，即无眼（Eya）和正弦（So），可促进从称为第二有丝分裂波（SMW）的终末细胞周期退出，从而实现分化。在寻找辅助因子的过程中，普遍表达的Combgap（Cg）是一种新型的转录伴侣，可以阻止细胞周期退出并特别在这种情况下干扰Eya-So活性。在这里，我们认为Cg可以作为一种灵活的转录平台，通过多种机制促进众多基因表达的结果。例如，Cg提供抑制活动，抑制Eya-So的输出，但不能像在其他情况下那样通过招募Polycomb染色质重塑复合物来抑制。我们建议主监管者既依赖于组装组合密码的明确表达的辅因子，也依赖于广泛表达的伴侣（如Cg），后者招募适当调节其靶增强子所需的多种分子活性。