Abstract
Although intergenic long noncoding RNAs (lincRNAs) have been linked to gene regulation in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here we identified 1,524 lincRNA clusters in 42 T cell samples, from early T cell progenitors to terminally differentiated helper T cell subsets. Our analysis revealed highly dynamic and cell-specific expression patterns for lincRNAs during T cell differentiation. These lincRNAs were located in genomic regions enriched for genes that encode proteins with immunoregulatory functions. Many were bound and regulated by the key transcription factors T-bet, GATA-3, STAT4 and STAT6. We found that the lincRNA LincR-Ccr2-5'AS, together with GATA-3, was an essential component of a regulatory circuit in gene expression specific to the TH2 subset of helper T cells and was important for the migration of TH2 cells.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Cell Differentiation
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Cell Movement
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GATA3 Transcription Factor / genetics
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GATA3 Transcription Factor / immunology
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GATA3 Transcription Factor / metabolism
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Gene Expression Regulation / immunology*
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Genetic Loci
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Annotation
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Precursor Cells, T-Lymphoid / cytology
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Precursor Cells, T-Lymphoid / immunology
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Precursor Cells, T-Lymphoid / metabolism*
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Protein Binding
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RNA, Long Noncoding / genetics*
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RNA, Long Noncoding / immunology
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STAT4 Transcription Factor / genetics
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STAT4 Transcription Factor / immunology
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STAT4 Transcription Factor / metabolism
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STAT6 Transcription Factor / genetics
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STAT6 Transcription Factor / immunology
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STAT6 Transcription Factor / metabolism
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Signal Transduction
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / immunology
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T-Box Domain Proteins / metabolism
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Th1 Cells / cytology
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Th1 Cells / immunology
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Th1 Cells / metabolism*
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Th17 Cells / cytology
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Th17 Cells / immunology
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Th17 Cells / metabolism*
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Th2 Cells / cytology
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Th2 Cells / immunology
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Th2 Cells / metabolism*
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Transcriptome / immunology
Substances
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GATA3 Transcription Factor
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Gata3 protein, mouse
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RNA, Long Noncoding
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STAT4 Transcription Factor
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STAT6 Transcription Factor
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Stat4 protein, mouse
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T-Box Domain Proteins
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T-box transcription factor TBX21