Combinatorial action of transcription factors (TFs) with partially overlapping expression is a widespread strategy to generate novel gene-expression patterns and, thus, cellular diversity. Known mechanisms underlying combinatorial activity require co-expression of TFs within the same cell. Here, we describe the mechanism by which two TFs that are never co-expressed generate a new, intersectional expression pattern in C. elegans embryos: lineage-specific priming of a gene by a transiently expressed TF generates a unique intersection with a second TF acting on the same gene four cell divisions later; the second TF is expressed in multiple cells but only activates transcription in those where priming occurred. Early induction of active transcription is necessary and sufficient to establish a competent state, maintained by broadly expressed regulators in the absence of the initial trigger. We uncover additional cells diversified through this mechanism. Our findings define a mechanism for combinatorial TF activity with important implications for generation of cell-type diversity.

具有部分重叠表达的转录因子（TF）的组合作用是一种广泛的策略，可产生新的基因表达模式，从而产生细胞多样性。组合活动背后的已知机制要求在同一细胞内共表达TF。在这里，我们描述了从未共表达的两个TF在秀丽隐杆线虫中生成新的交叉表达模式的机制。胚胎：通过瞬时表达的TF对基因的谱系特异性引物与作用于同一基因的第二个TF在四个细胞分裂后产生独特的交叉。第二个TF在多个细胞中表达，但仅在发生启动反应的细胞中激活转录。尽早地诱导主动转录是建立足够的状态所必需和充分的，在没有初始触发的情况下，由广泛表达的调节子维持这种状态。我们发现通过这种机制多样化的其他细胞。我们的发现确定了组合TF活性的机制，对细胞类型多样性的产生具有重要意义。