Schwann cell regulation by NR2F2 using Cut&Run

We focused on NR2F1 and NR2F2 (CoupTF1/CoupTF2) since they are expressed from neural crest through Schwann cell maturity, and found that knockdown of nuclear receptors Nr2f1 and Nr2f2 in primary Schwann cells downregulated genes such as Myelin Basic Protein (Mbp), Desert Hedgehog (Dhh), and N-Myc Downstream Regulated 1 (Ndrg1). In this study, we have elucidated a NR2F-regulated target gene network in Schwann cells, which revealed enrichment for non-myelinating Schwann cell genes. We used Cut&Run in S16 Schwann cells to show novel, genome-wide binding sites of NR2F1/2 and downstream transcription factors, YY1, SREBP1, Retinoid X Receptor (RXRG) and TEA-Domain factor (TEAD1). Our study elucidates the transcriptional cooperation that forms unique enhancer landscapes and the regulatory network that targets non-myelinating Schwann cells.本研究聚焦于核受体NR2F1与NR2F2（CoupTF1/CoupTF2），因其在神经嵴至施万细胞成熟的全过程中均有表达。我们发现，在原代施万细胞中敲低Nr2f1与Nr2f2的表达，会下调髓鞘碱性蛋白（Mbp）、沙漠刺猬因子（Dhh）以及N-Myc下游调控蛋白1（Ndrg1）等基因的表达水平。本研究阐明了施万细胞中受NR2F调控的靶基因网络，该网络显著富集非髓鞘化施万细胞相关基因。我们通过在S16施万细胞系中应用切口释放技术（Cut&Run），绘制了NR2F1/2以及下游转录因子YY1、固醇调节元件结合蛋白1（SREBP1）、维甲酸X受体（RXRG）与TEA结构域转录因子1（TEAD1）的全基因组新型结合位点。本研究揭示了构建独特增强子景观的转录协同机制，以及靶向非髓鞘化施万细胞的调控网络。