RNF138 inhibits late inflammatory gene transcription through degradation of SMARCC1 of SWI/SNF complex

As one of the core components of the SWI/SNF complex, SMARCC1 (SAF155, SRG3) plays essential role in activation of the late inflammatory genes in response to microbial challenge. However, little is known about the mechanisms how SMARCC1 is regulated in innate response. Here, we identify for the first time that nuclear E3 ubiquitin ligase RNF138 acts as a critical negative regulator in inflammatory responses. RNF138 selectively interacts with SMARCC1 and mediates its K48-linked polyubiquitination at position Lys643 and proteasomal degradation. As a result, catalytic activity of RNF138 fine-tunes the kinetics of late inflammatory gene transcription by inhibiting persistent chromatin remodeling at SWI/SNF regulated gene loci. These results provide mechanistic insight into the interplay among nucleosome remodeling, inflammation and ubiquitylation, and underscore the critical role of the E3 ligases in controlling both extent and duration of inflammatory responses. We analyzed and compared the inflammatory genes expression with results obtained from two RNA-seq data of wild type and RNF138 deficient RAW264.7 cells after LPS treatment (100ng/ml) for 3 hours.