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

Shibin Ma, Zhenping Ming, Ai Yu Gong, Yang Wang, Xiqiang Chen, Guoku Hu, Rui Zhou, Annemarie Shibata, Patrick Swanson, Xian-Ming Chen

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 a-induced protein 3 (Tnfaip3) gene, is an early-primary response gene controlled by nuclear factor-kB (NF-κB) 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-κB-regulated inflammatory genes in response to bacterial LPSs stimulation. LincRNA-Tnfaip3 physically interacts with the high-mobility group box 1 (Hmgb1), assembling a NF-κB/Hmgb1/lincRNA-Tnfaip3 complex in macrophages after LPS stimulation. This resultant NF-κB/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-κBinduced lincRNA-Tnfaip3 to act as a coactivator of NF-κB for the transcription of inflammatory genes in innate immune cells throughmodulation of epigenetic chromatin remodeling.

Original languageEnglish (US)
Pages (from-to)1215-1225
Number of pages11
JournalFASEB Journal
Volume31
Issue number3
DOIs
StatePublished - Mar 1 2017

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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