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

Nature Immunology volume 14, pages 11901198 (2013) | Download Citation

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.

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Acknowledgements

We thank the DNA Sequencing Core facility of the National Heart, Lung and Blood Institute (NHLBI) for sequencing the ChIP-Seq and RNA-Seq libraries; J. Edwards for most cell-sorting experiments; the flow cytometry core of NHLBI for some cell-sorting experiments and analysis; H. Cao for comments on the knockdown of lincRNA by shRNA; D. Northrup for critical reading and editing of the manuscript; H. Zhang for sharing experience with chemokines and chemokine receptors; P. Burr for RNA-Seq; and X. Zheng for sharing code for binomial tests. This study used the Biowulf Linux cluster of the US National Institutes of Health. Supported by the Division of Intramural Research of the NHLBI and NIAID (US National Institutes of Health).

Author information

Author notes

    • Gangqing Hu
    • , Qingsong Tang
    •  & Suveena Sharma

    These authors contributed equally to this work.

Affiliations

  1. Systems Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.

    • Gangqing Hu
    • , Qingsong Tang
    •  & Keji Zhao
  2. Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

    • Suveena Sharma
    • , Fang Yu
    • , Thelma M Escobar
    • , Stefan A Muljo
    •  & Jinfang Zhu

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Contributions

G.H., J.Z. and K.Z. conceived of the study, designed experiments and data analysis, and wrote the manuscript; Q.T., S.S. and F.Y. did experiments and edited the manuscript; G.H. analyzed the data; and T.M.E. and S.A.M. contributed RNA-Seq data for STAT4-deficient TH1 cells, STAT6-deficient TH2 cells and the corresponding wild-type TH1 and TH2 cells.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jinfang Zhu or Keji Zhao.

Supplementary information

Word documents

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–7 and Supplementary Tables 2–6 and 8–9

Excel files

  1. 1.

    Supplementary Table 1

    A compilation of lincRNAs during T cell development and differentiation.

  2. 2.

    Supplementary Table 7

    Th2-preferred genes affected by LincR-Ccr2-5'AS knockdown in TH2 cells

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DOI

https://doi.org/10.1038/ni.2712

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