Journal
JOURNAL OF IMMUNOLOGY
Volume 193, Issue 8, Pages 3959-3965Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1401099
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Funding
- National Institutes of Health [R01 AI044924, T32 AR059039]
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Long noncoding RNAs (lncRNAs), critical regulators of protein-coding genes, are likely to be coexpressed with neighboring protein-coding genes in the genome. How the genome integrates signals to achieve coexpression of lncRNA genes and neighboring protein-coding genes is not well understood. The IncRNA Tmevpg1 (NeST, Ifng-AS1) is critical for Th1-lineage-specific expression of Ifng and is coexpressed with Ifng. In this study, we show that T-bet guides epigenetic remodeling of Tmevpg1 proximal and distal enhancers, leading to recruitment of stimulus-inducible transcription factors, NF-kappa B and Ets-1, to the locus. Activities of Tmevpg1-specific enhancers and Tmevpg1 transcription are dependent upon NF-kappa B. Thus, we propose that T-bet stimulates epigenetic remodeling of Tmevpg1-specific enhancers and Ifng-specific enhancers to achieve Th1-lineage-specific expression of Ifng.
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