Regulation of the Th1 Genomic Locus from Ifng through Tmevpg1 by T-bet

被引：98

作者：

Collier, Sarah P. ^{[1
]}

Henderson, Melodie A. ^{[2
]}

Tossberg, John T. ^{[2
]}

Aune, Thomas M. ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA

来源：

JOURNAL OF IMMUNOLOGY | 2014年 / 193卷 / 08期

基金：

美国国家卫生研究院;

关键词：

LONG NONCODING RNA; INTERFERON-GAMMA LOCUS; CELL-DIFFERENTIATION; GENE-EXPRESSION; TRANSCRIPTION FACTOR; EPIGENETIC CONTROL; NATURAL-KILLER; CHROMATIN; PROMOTER; RESPONSES;

D O I：

10.4049/jimmunol.1401099

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：3959 / 3965

页数：7

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