LincRNA‐Cox2 modulates TNF‐α‐induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi‐2/NuRD‐mediated epigenetic histone modifications

• Published in: The FASEB journal 2016-03, Vol.30 (3), p.1187-1197
• Main Authors: Tong, Qiang, Gong, Ai‐Yu, Zhang, Xin‐Tian, Lin, Chengchi, Ma, Shibin, Chen, Jing, Hu, Guoku, Chen, Xian‐Ming
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Cell Line; Cyclooxygenase 2 - metabolism; Down-Regulation; Epigenomics - methods; Epithelial Cells - metabolism; H12b; histone modifications; Histones - genetics; Interleukin-12 - genetics; Interleukin-12 - metabolism; intestinal epithelium; Intestines - metabolism; LincRNAs; Mi-2 Nucleosome Remodeling and Deacetylase Complex - genetics; Mi-2 Nucleosome Remodeling and Deacetylase Complex - metabolism; Mice; Mice, Inbred C57BL; Mi‐2/NuRD complex; NF-kappa B - metabolism; Nucleosomes - genetics; Promoter Regions, Genetic; Research Communication; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Transcription, Genetic; Transcriptional Activation; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.15-279166

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 upregulation 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‐κB 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 (Mi2/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.—Tong, Q., Gong, A.‐Y., Zhang, X.‐T., Lin, C., Ma, S., Chen, J., Hu, G., Chen, X.‐M. LincRNA‐Cox2 modulates TNF‐α‐induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi‐2/NuRD‐mediated epigenetic histone modifications. FASEB J. 30, 1187–1197 (2016). www.fasebj.org