SWI/SNF and NuRD are protein complexes that antagonistically regulate DNA accessibility. However, repression of their activities often leads to unanticipated changes in target gene expression (paradoxical), highlighting our incomplete understanding of their activities. Here we show that SWI/SNF and NuRD are in a tug-of-war to regulate PRC2 occupancy at lowly expressed and bivalent genes in mouse embryonic stem cells (mESCs). In contrast, at promoters of average or highly expressed genes, SWI/SNF and NuRD antagonistically modulate RNA polymerase II (Pol II) release kinetics, arguably owing to accompanying alterations in H3.3 and H2A.Z levels at promoter-flanking nucleosomes, leading to paradoxical changes in gene expression. Owing to this mechanism, the relative activities of the two remodelers potentiate gene promoters toward Pol II–dependent open or PRC2-dependent closed chromatin states. Our results highlight RNA Pol II occupancy as the key parameter in determining the direction of gene expression changes in response to SWI/SNF and NuRD inactivation at gene promoters in mESCs.

中文翻译：

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SWI/SNF 和 NuRD 失活对基因表达的影响与启动子处 RNA 聚合酶 II 的占据水平紧密相关

SWI/SNF 和 NuRD 是拮抗调节 DNA 可及性的蛋白质复合物。然而，抑制它们的活动通常会导致目标基因表达的意外变化（自相矛盾），这突出了我们对它们活动的不完全理解。在这里，我们表明 SWI/SNF 和 NuRD 正在进行拉锯战，以调节小鼠胚胎干细胞 (mESC) 中低表达和二价基因的 PRC2 占用。相反，在平均或高表达基因的启动子上，SWI/SNF 和 NuRD 拮抗调节 RNA 聚合酶 II (Pol II) 释放动力学，可以说是由于启动子侧翼核小体 H3.3 和 H2A.Z 水平的伴随改变，导致基因表达的矛盾变化。由于这种机制，两种重塑剂的相对活性增强了基因启动子对 Pol II 依赖性开放或 PRC2 依赖性封闭染色质状态的影响。我们的结果强调 RNA Pol II 占据是确定基因表达变化方向的关键参数，以响应 mESC 中基因启动子的 SWI/SNF 和 NuRD 失活。