title: A long noncoding RNA, lincRNA-Tnfaip3, acts as a coregulator of NF-κB to modulate inflammatory gene transcription in mouse macrophages.
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 genelincRNA-Tnfaip3, located at mouse chromosome 10 proximal to the tumor necrosis factor α-induced protein 3 (Tnfaip3) 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.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Shibin
authors.initials: S
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Ming
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Ai-Yu
authors.initials: AY
authors.lastname: Gong
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Guoku
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Hubei, China; and.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Biology, College of Arts and Sciences, Creighton University, Omaha, Nebraska, USA.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Swanson
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USA; xianmingchen@creighton.edu.
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D024243:HMGB1 Protein / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000235:genetics
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D006657:Histones; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; C513261:Tnfaip3 protein, mouse
keywords: Hmgb1; histone modifications; inflammation; lincRNAs