SOX4 and RELA function as transcriptional partners to regulate the expression of TNF-responsive genes in fibroblast-like synoviocytes [RNA-Seq]

Purpose: Our goal was to evaluate the transcriptional profiles of FLS. We used genome wide approaches to uncover the interactions between SOXC transcription factors and RELA/p65 transcription factor, downstream of TNF signaling. Methods: We analyzed RNA-seq of TNF-treated FLS in control and SOXC gene knockout backgrounds. FLS isolated from Sox4fl/fl 11fl/fl 12fl/fl mice were transduced with Ade5CMV-eGFP virus for controls or transduced with Ade5CMV-Cre adenovirus for knockout of the three SOXC family genes, Sox4, Sox11 and Sox12 Results: paired-end reads were mapped to the mm10 genome assembly. RNA levels were normalized using DESeq. Conclusion: SOXC family genes regulate TNF mediated gene expression. Overall design: Identification of SOXC-dependent and independent aspects of the TNF-regulated transcriptome.

研究目的：本研究旨在评估成纤维样滑膜细胞（FLS）的转录谱，通过全基因组学方法揭示肿瘤坏死因子（TNF）信号通路下游SOXC转录因子与RELA/p65转录因子之间的相互作用。
研究方法：我们针对TNF处理后的成纤维样滑膜细胞（FLS），分别设置对照组与SOXC基因敲除背景组，开展RNA测序（RNA-seq）分析。从Sox4fl/fl、Sox11fl/fl及Sox12fl/fl小鼠中分离得到的FLS，以Ade5CMV-eGFP病毒转导作为对照组，或以Ade5CMV-Cre腺病毒转导以敲除Sox4、Sox11及Sox12这三个SOXC家族基因。
研究结果：将双端测序读段比对至mm10基因组组装版本，采用DESeq对RNA表达水平进行标准化处理。
研究结论：SOXC家族基因可调控TNF介导的基因表达。
整体实验设计：鉴定TNF调控转录组中SOXC依赖性与非依赖性的相关特征。