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Abstract：
Pioneer transcription factors (TFs) regulate cell fate by establishing transcriptionally primed and active states. However, cell fate control requires the coordination of both lineage-specific gene activation and repression of alternative-lineage programs, a process that is poorly understood. Here, we demonstrate that the pioneer TF FOXA coordinates with PRDM1 TF to recruit nucleosome remodeling and deacetylation (NuRD) complexes and Polycomb repressive complexes (PRCs), which establish highly occupied, accessible nucleosome conformation with bivalent epigenetic states, thereby preventing precocious and alternative-lineage gene expression during human endoderm differentiation. Similarly, the pioneer TF OCT4 coordinates with PRDM14 to form bivalent enhancers and repress cell differentiation programs in human pluripotent stem cells, suggesting that this may be a common and critical function of pioneer TFs. We propose that pioneer and PRDM TFs coordinate to safeguard cell fate through epigenetic repression mechanisms.
摘要：
先锋转录因子（TF）通过建立转录引发和活性状态来调节细胞命运。然而,细胞命运控制需要协调谱系特异性基因激活和替代谱系程序的抑制，这是一个鲜为人知的过程。这里,我们证明了先驱TFFOXA与PRDM1TF协调以募集核小体重塑和去乙酰化（NuRD）复合物和Polycomb抑制复合物（PRCs），建立高度占用的，具有二价表观遗传状态的可接近核小体构象，从而防止人类内胚层分化过程中的早熟和替代谱系基因表达。同样，先驱TFOCT4与PRDM14协调形成二价增强子并抑制人类多能干细胞中的细胞分化程序，这表明这可能是先驱TFs的共同和关键功能。我们建议先驱和PRDMTFs通过表观遗传抑制机制协调保护细胞命运。
