Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a “reader” of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC (mESC) pluripotency since knockdown of Npac causes mESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our chromatin immunoprecipitation followed by sequencing (ChIP-seq) results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with positive transcription elongation factor b (p-TEFb), Ser2-phosphorylated RNA Pol II (RNA Pol II Ser2P), and Ser5-phosphorylated RNA Pol II (RNA Pol II Ser5P). Furthermore, depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1. Taken together, we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA Pol II Ser2P and Ser5P.

染色质修饰有助于胚胎干细胞 (ESC) 的多能性维持。然而，相关机制仍然模糊不清。在这里，我们表明Npac是组蛋白 H3 赖氨酸 36 三甲基化 (H3K36me3) 的“读取器”，它是维持小鼠 ESC (mESC) 多能性所必需的，因为Npac的敲低会导致 mESC 分化。小鼠胚胎成纤维细胞 (MEF) 中 Npac 的消耗抑制了重编程效率。此外，我们的染色质免疫沉淀和 Npac 测序 (ChIP-seq) 结果表明 Npac 与组蛋白H3K36me3 共定位在 mESCs 中活跃转录基因的基因体中。有趣的是，我们发现 Npac 与正转录延伸因子 b (p-TEFb)、Ser2-磷酸化 RNA Pol II (RNA Pol II Ser2P) 和 Ser5-磷酸化 RNA Pol II (RNA Pol II Ser5P) 相互作用。此外，Npac 的消耗会破坏多能性基因Nanog和Rif1的转录延伸。总之，我们提出 Npac 通过募集 p-TEFb 并与 RNA Pol II Ser2P 和 Ser5P 相互作用，对多能性基因的转录延伸至关重要。