Expression and regulation of intergenic long noncoding RNAs during T cell development and differentiation

Nat Immunol. 2013 Nov;14(11):1190-8. doi: 10.1038/ni.2712. Epub 2013 Sep 22.

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

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / immunology
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation / immunology*
  • Genetic Loci
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Annotation
  • Precursor Cells, T-Lymphoid / cytology
  • Precursor Cells, T-Lymphoid / immunology
  • Precursor Cells, T-Lymphoid / metabolism*
  • Protein Binding
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / immunology
  • STAT4 Transcription Factor / genetics
  • STAT4 Transcription Factor / immunology
  • STAT4 Transcription Factor / metabolism
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / immunology
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / immunology
  • T-Box Domain Proteins / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism*
  • Transcriptome / immunology

Substances

  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • RNA, Long Noncoding
  • STAT4 Transcription Factor
  • STAT6 Transcription Factor
  • Stat4 protein, mouse
  • T-Box Domain Proteins
  • T-box transcription factor TBX21

Associated data

  • GEO/GSE48138