A long noncoding RNA, lincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages

Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein-coding genes. We report here that the lincRNA gene lincRNA-Tnfaip3, located at mouse chromosome 10 proximal to the tumor necrosis factor alpha-induced protein 3 (Tnfaip3) gene, is an early-primary response gene controlled by nuclear factor-kappa B (NF-kappa B) signaling in murine macrophages. Functionally, lincRNA-Tnfaip3 appears to mediate both the activation and repression of distinct classes of inflammatory genes in macrophages. Specifically, induction of lincRNA-Tnfaip3 is required for the transactivation of NF-kappa B-regulated inflammatory genes in response to bacterial LPSs stimulation. LincRNA-Tnfaip3 physically interacts with the high-mobility group box 1 (Hmgb1), assembling a NF-kappa B/Hmgb1/lincRNA-Tnfaip3 complex in macrophages after LPS stimulation. This resultantNF-kappa B/Hmgb1/lincRNA-Tnfaip3 complex can modulate Hmgb1-associated histone modifications and, ultimately, transactivation of inflammatory genes in mouse macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role of NF-kappa Binduced lincRNA-Tnfaip3 to act as a coactivator of NF-kappa B for the transcription of inflammatory genes in innate immune cells throughmodulation of epigenetic chromatin remodeling.- Ma, S., Ming, Z., Gong, A.- Y., Wang, Y., Chen, X., Hu, G., Zhou, R., Shibata, A., Swanson, P. C., Chen, X.- M. A long noncoding RNA, LincRNA- Tnfaip3, acts as a coregulator of NF- kB to modulate inflammatory gene transcription in mouse macrophages.