Ma Shibin, Ming Zhenping, Gong Ai-Yu, Wang Yang, Chen Xiqiang, Hu Guoku, Zhou Rui, Shibata Annemarie, Swanson Patrick C, Chen Xian-Ming
Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Hubei, China; and.
FASEB J. 2017 Mar;31(3):1215-1225. doi: 10.1096/fj.201601056R. Epub 2016 Dec 15.
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 , located at mouse chromosome 10 proximal to the tumor necrosis factor α-induced protein 3 () gene, is an early-primary response gene controlled by nuclear factor-κB (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-κB-induced lincRNA-Tnfaip3 to act as a coactivator of NF-κB for the transcription of inflammatory genes in innate immune cells through modulation 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-κB to modulate inflammatory gene transcription in mouse macrophages.
长链基因间非编码RNA（lincRNA）是来自注释的蛋白质编码基因的基因间区域的长链非编码转录本（>200 nt）。我们在此报告，位于小鼠10号染色体上肿瘤坏死因子α诱导蛋白3（Tnfaip3）基因附近的lincRNA基因，是小鼠巨噬细胞中由核因子κB（NF-κB）信号传导控制的早期初级反应基因。在功能上，lincRNA-Tnfaip3似乎介导巨噬细胞中不同类别的炎症基因的激活和抑制。具体而言，响应细菌脂多糖刺激，NF-κB调节的炎症基因的反式激活需要lincRNA-Tnfaip3的诱导。LincRNA-Tnfaip3与高迁移率族蛋白盒1（Hmgb1）发生物理相互作用，在脂多糖刺激后在巨噬细胞中组装NF-κB/Hmgb1/lincRNA-Tnfaip3复合物。这种产生的NF-κB/Hmgb1/lincRNA-Tnfaip3复合物可以调节与Hmgb1相关的组蛋白修饰，并最终调节小鼠巨噬细胞中炎症基因对微生物攻击的反式激活。因此，我们的数据表明NF-κB诱导的lincRNA-Tnfaip3通过调节表观遗传染色质重塑，作为先天性免疫细胞中NF-κB的共激活因子对炎症基因转录发挥新的调节作用。-马，S.，明，Z.，龚，A.-Y.，王，Y.，陈，X.，胡，G.，周，R.，柴田，A.，斯旺森，P.C.，陈，X.-M. 一种长链非编码RNA，LincRNA-Tnfaip3，作为NF-κB的共调节因子调节小鼠巨噬细胞中的炎症基因转录。
