title: LincRNA-Cox2 Promotes Late Inflammatory Gene Transcription in Macrophages through Modulating SWI/SNF-Mediated Chromatin Remodeling.
abstract: Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein-coding genes. One of the most highly induced lincRNAs in macrophages upon TLR ligation is lincRNA-Cox2, which was recently shown to mediate the activation and repression of distinct classes of immune genes in innate immune cells. We report that lincRNA-Cox2, located at chromosome 1 proximal to the PG-endoperoxide synthase 2 (Ptgs2/Cox2) gene, is an early-primary inflammatory gene controlled by NF-κB signaling in murine macrophages. Functionally, lincRNA-Cox2 is required for the transcription of NF-κB-regulated late-primary inflammatory response genes stimulated by bacterial LPS. Specifically, lincRNA-Cox2 is assembled into the switch/sucrose nonfermentable (SWI/SNF) complex in cells after LPS stimulation. This resulting lincRNA-Cox2/SWI/SNF complex can modulate the assembly of NF-κB subunits to the SWI/SNF complex, and ultimately, SWI/SNF-associated chromatin remodeling and transactivation of the late-primary inflammatory-response genes in macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role for NF-κB-induced lincRNA-Cox2 as a coactivator of NF-κB for the transcription of late-primary response genes in innate immune cells through modulation of epigenetic chromatin remodeling.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.|School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China.
authors.forename: Guoku
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Ai-Yu
authors.initials: AY
authors.lastname: Gong
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Shibin
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Su
authors.affiliation: Department of Biology, Creighton University College of Arts and Sciences, Omaha, NE 68178, USA.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Chemistry, Creighton University College of Arts and Sciences, Omaha, NE 68178, USA.
authors.forename: Juliane K
authors.initials: JK
authors.lastname: Strauss-Soukup
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Drescher
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D008070:Lipopolysaccharides; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D051546:Cyclooxygenase 2