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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE197694 | GEO | 2022/03/21

REPOSITORIES: GEO

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SOX4 and RELA Function as Transcriptional Partners to Regulate the Expression of TNF- Responsive Genes in Fibroblast-Like Synoviocytes.

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

Project description: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.

2022-03-21 | GSE197691 | GEO

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

Project description:Purpose: Our goal was to evaluate the transcriptional profiles of FLS. We used genome wide approaches to uncover the interactions between SOX4 and RELA/p65, downstream of TNF signaling. Methods: ChIP-seq of mouse FLS was used to compare the global DNA binding profiles of SOX4 and RELA. Results: ChIP-seq revealed an overllap of SOX4 peak summits with RELA peak summits suggesting that both proteins bind in close-proximity on regulatory sequences, enabling them to co-operatively regulate gene expression. By integrating the ChIP-seq results with RNA-seq from SoxC-knockout FLS we identified a set of TNF-responsive genes that are targets of the RELA-SOX4 transcriptional complex. Conclusion: SOX4 and RELA, together orchestrate a multimodal regulation of gene expression downstream of TNF signaling. Their interdependent activities play a pivotal role in the transformation FLS in arthritis and in the inflammatory pathology of diverse tissues where RELA and SOX4 are co-expressed.

2022-03-21 | GSE197491 | GEO

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Project description:SOX4 and RELA function as transcriptional partners to regulate the expression of TNF-responsive genes in fibroblast-like synoviocytes

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

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Project description:This SuperSeries is composed of the SubSeries listed below.