Although the in vitro structural and in vivo spatial characteristics of transcription factor (TF) binding are well defined, TF interactions with chromatin and other companion TFs during development are poorly understood. To analyze such interactions in vivo, we profiled several TFs across a time course of human embryonic stem cell differentiation and studied their interactions with nucleosomes and co-occurring TFs by enhanced chromatin occupancy (EChO), a computational strategy for classifying TF interactions with chromatin. EChO shows that multiple individual TFs can employ either direct DNA binding or "pioneer" nucleosome binding at different enhancer targets. Nucleosome binding is not exclusively confined to inaccessible chromatin but rather correlated with local binding of other TFs and degeneracy at key bases in the pioneer factor target motif responsible for direct DNA binding. Our strategy reveals a dynamic exchange of TFs at enhancers across developmental time that is aided by pioneer nucleosome binding.

中文翻译：

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分化过程中的先锋因子-核小体结合事件是基序编码的。

尽管转录因子 (TF) 结合的体外结构和体内空间特征已明确，但对转录因子在发育过程中与染色质和其他伴随 TF 的相互作用知之甚少。为了分析体内的这种相互作用，我们分析了人类胚胎干细胞分化过程中的几个转录因子，并通过增强染色质占有率（EChO）（一种对转录因子与染色质相互作用进行分类的计算策略）研究了它们与核小体和共存转录因子的相互作用。EChO 表明，多个单独的 TF 可以在不同的增强子靶点上采用直接 DNA 结合或“先锋”核小体结合。核小体结合不仅限于难以接近的染色质，还与其他 TF 的局部结合以及负责直接 DNA 结合的先锋因子靶基序中关键碱基的简并性相关。我们的策略揭示了在整个发育过程中增强子处转录因子的动态交换，这是在先驱核小体结合的帮助下进行的。