title: Regulation of the Th1 genomic locus from Ifng through Tmevpg1 by T-bet.
abstract: 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 lncRNA 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-κB and Ets-1, to the locus. Activities of Tmevpg1-specific enhancers and Tmevpg1 transcription are dependent upon NF-κB. 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.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Collier
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: Melodie A
authors.initials: MA
authors.lastname: Henderson
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: John T
authors.initials: JT
authors.lastname: Tossberg
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232 tom.aune@vanderbilt.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Aune
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D004742:Enhancer Elements, Genetic; D044127:Epigenesis, Genetic; D056426:Genetic Loci; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D051996:Transcription Factor RelA / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D062085:RNA, Long Noncoding; C498144:Rela protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C000594242:Tmevpg1 long noncoding RNA, mouse; D051996:Transcription Factor RelA; D007371:Interferon-gamma