title: LincRNA-Cox2 modulates TNF-α-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications.
abstract: Long intergenic noncoding RNAs (lincRNAs) can regulate the transcription of inflammatory genes and thus may represent a new group of inflammatory mediators with a potential pathogenic role in inflammatory diseases. Here, our genome-wide transcriptomic data show that TNF-α stimulation caused up-regulation of 171 lincRNAs and down-regulation of 196 lincRNAs in murine intestinal epithelial cells in culture. One of the up-regulated lincRNAs, lincRNA-Cox2, is an early-responsive lincRNA induced by TNF-α through activation of the NF-ĸB signaling pathway. Knockdown of lincRNA-Cox2 resulted in reprogramming of the gene expression profile in intestinal epithelial cells in response to TNF-α stimulation. Specifically, lincRNA-Cox2 silencing significantly (P < 0.05) enhanced the transcription of Il12b, a secondary late-responsive gene induced by TNF-α. Mechanistically, lincRNA-Cox2 promoted the recruitment of the Mi-2/nucleosome remodeling and deacetylase (Mi-2/NuRD) repressor complex to the Il12b promoter region. Recruitment of the Mi-2/NuRD complex was associated with decreased H3K27 acetylation and increased H3K27 dimethylation at the Il12b promoter region, which might contribute to Il12b trans-suppression by lincRNA-Cox2. Thus, our data demonstrate a novel mechanism of epigenetic modulation by lincRNA-Cox2 on Il12b transcription, supporting an important role for lincRNAs in the regulation of intestinal epithelial inflammatory responses.
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tong
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Ai-Yu
authors.initials: AY
authors.lastname: Gong
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xin-Tian
authors.initials: XT
authors.lastname: Zhang
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Chengchi
authors.initials: C
authors.lastname: Lin
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Shibin
authors.initials: S
authors.lastname: Ma
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Guoku
authors.initials: G
authors.lastname: Hu
authors.affiliation: *Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska, USA; Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and School of Medicine, University of Electronic Science and Technology of China, Chengdu, China xianmingchen@creighton.edu.
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015536:Down-Regulation; D057890:Epigenomics / Q000379:methods; D004847:Epithelial Cells / Q000378:metabolism; D006657:Histones / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D006657:Histones; D016328:NF-kappa B; D009707:Nucleosomes; D062085:RNA, Long Noncoding; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: Il12b; LincRNAs; Mi-2/NuRD complex; histone modifications; intestinal epithelium