biostudies-literatureJones KNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAMS NIH HHS789349https://www.ebi.ac.uk/biostudies/studies/S-EPMC9074688biostudies-literatureUnknown13SOX4 belongs to the group C of the SOX transcription factor family. It is a critical mediator of tumor necrosis factor alpha (TNF)-induced transformation of fibroblast-like s-ynoviocytes (FLS) in arthritis. In this study we investigated the genome wide association between the DNA binding and transcriptional activities of SOX4 and the NF-kappaB signaling transcription factor RELA/p65 downstream of TNF signaling. We used ChIP-seq assays in mouse FLS to compare the global DNA binding profiles of SOX4 and RELA. RNA-seq of TNF-induced wildtype and <i>SoxC</i>-knockout FLS was used to identify the SOX4-dependent and independent aspects of the TNF-regulated transcriptome. We found that SOX4 and RELA physically interact with each other on the chromatin. Interestingly, ChIP-seq assays revealed thatFrontiers in immunologySOX4 and RELA Function as Transcriptional Partners to Regulate the Expression of TNF- Responsive Genes in Fibroblast-Like Synoviocytes.PMC9074688R01 AR070736Niu SJones KBhattaram PRamirez-Perez SDrissi HGangishetti UfalseSOX4 and RELA Function as Transcriptional Partners to Regulate the Expression of TNF- Responsive Genes in Fibroblast-Like Synoviocytes.SOX4 belongs to the group C of the SOX transcription factor family. It is a critical mediator of tumor necrosis factor alpha (TNF)-induced transformation of fibroblast-like s-ynoviocytes (FLS) in arthritis. In this study we investigated the genome wide association between the DNA binding and transcriptional activities of SOX4 and the NF-kappaB signaling transcription factor RELA/p65 downstream of TNF signaling. We used ChIP-seq assays in mouse FLS to compare the global DNA binding profiles of SOX4 and RELA. RNA-seq of TNF-induced wildtype and <i>SoxC</i>-knockout FLS was used to identify the SOX4-dependent and independent aspects of the TNF-regulated transcriptome. We found that SOX4 and RELA physically interact with each other on the chromatin. Interestingly, ChIP-seq assays revealed that2022-01-01T00:00:00Z20222026-07-14T16:44:55.02Z2025-02-19T03:27:37.723ZS-EPMC90746883552985210.3389/fimmu.2022.789349