RNA-seq analysis of S16 Schwann cells treated with siRNA for Nr2f1/Nr2f2 (CoupTFI/CoupTFII)

In a previous study, we had compared SOX10-bound regulatory elements in Schwann cells and oligodendrocytes, and we identified a specific enrichment for nuclear receptor motifs at SOX10 binding sites in Schwann cells. We initially 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) and Desert Hedgehog (Dhh). In this study, we have elucidated a NR2F-regulated target gene network in Schwann cells, which revealed enrichment for non-myelinating Schwann cell genes. Cut&Run assays in S16 Schwann cells revealed novel, genome-wide binding sites of NR2F1/2 and downstream transcription factors, Retinoid X Receptor (RXRG) and TEA-Domain factor (TEAD1).既往研究中，我们曾比较施万细胞（Schwann cells）与少突胶质细胞（oligodendrocytes）中SOX10结合的调控元件，并发现施万细胞内SOX10结合位点存在核受体基序的特异性富集。我们最初将研究焦点置于NR2F1与NR2F2（即CoupTF1/CoupTF2），因其表达覆盖从神经嵴阶段直至施万细胞成熟的全过程，并发现原代施万细胞中敲低核受体Nr2f1与Nr2f2会下调髓鞘碱性蛋白（Myelin Basic Protein，Mbp）、沙漠刺猬因子（Desert Hedgehog，Dhh）等基因的表达。本研究中，我们阐明了施万细胞内受NR2F调控的靶基因网络，该网络显示非髓鞘化施万细胞相关基因存在富集。对S16施万细胞开展的Cut&Run实验（Cut&Run assays）揭示了NR2F1/2及其下游转录因子维甲酸X受体（Retinoid X Receptor，RXRG）与TEA结构域因子（TEA-Domain factor，TEAD1）的全新全基因组结合位点。