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

Qiang Tong, Ai Yu Gong, Xin Tian Zhang, Chengchi Lin, Shibin Ma, Jing Chen, Guoku Hu, Xian-Ming Chen

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 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 (Mi-2/NuRD) repressor complex tothe 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.

Original languageEnglish
Pages (from-to)1187-1197
Number of pages11
JournalFASEB Journal
Volume30
Issue number3
DOIs
StatePublished - Mar 1 2016

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Histone Code
Long Noncoding RNA
Nucleosomes
Transcription
Epigenomics
Histones
Untranslated RNA
Genes
Epithelial Cells
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Genetic Promoter Regions
Acetylation
Gene expression
Chemical activation
Modulation
Transcriptome

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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LincRNA-Cox2 modulates TNF-α-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications. / Tong, Qiang; Gong, Ai Yu; Zhang, Xin Tian; Lin, Chengchi; Ma, Shibin; Chen, Jing; Hu, Guoku; Chen, Xian-Ming.

In: FASEB Journal, Vol. 30, No. 3, 01.03.2016, p. 1187-1197.

Research output: Contribution to journalArticle

Tong, Qiang ; Gong, Ai Yu ; Zhang, Xin Tian ; Lin, Chengchi ; Ma, Shibin ; Chen, Jing ; Hu, Guoku ; Chen, Xian-Ming. / LincRNA-Cox2 modulates TNF-α-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications. In: FASEB Journal. 2016 ; Vol. 30, No. 3. pp. 1187-1197.
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